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

Vortices on Orbifolds

The Abelian and non-Abelian vortices on orbifolds are investigated based on the moduli matrix approach, which is a powerful method to deal with the BPS equation. The moduli space and the vortex collision are discussed through the moduli matrix as well as the regular space. It is also shown that a quiver structure is found in the Kahler quotient, and a half of ADHM is obtained for the vortex theory on the orbifolds as the case before orbifolding.Comment: 25 pages, 4 figures; references adde

Different Pattern of Immunoglobulin Gene Usage by HIV-1 Compared to Non-HIV-1 Antibodies Derived from the Same Infected Subject

A biased usage of immunoglobulin (Ig) genes is observed in human anti-HIV-1 monoclonal antibodies (mAbs) resulting probably from compensation to reduced usage of the VH3 family genes, while the other alternative suggests that this bias usage is due to antigen requirements. If the antigen structure is responsible for the preferential usage of particular Ig genes, it may have certain implications for HIV vaccine development by the targeting of particular Ig gene-encoded B cell receptors to induce neutralizing anti-HIV-1 antibodies. To address this issue, we have produced HIV-1 specific and non-HIV-1 mAbs from an infected individual and analyzed the Ig gene usage. Green-fluorescence labeled virus-like particles (VLP) expressing HIV-1 envelope (Env) proteins of JRFL and BaL and control VLPs (without Env) were used to select single B cells for the production of 68 recombinant mAbs. Ten of these mAbs were HIV-1 Env specific with neutralizing activity against V3 and the CD4 binding site, as well as non-neutralizing mAbs to gp41. The remaining 58 mAbs were non-HIV-1 Env mAbs with undefined specificities. Analysis revealed that biased usage of Ig genes was restricted only to anti-HIV-1 but not to non-HIV-1 mAbs. The VH1 family genes were dominantly used, followed by VH3, VH4, and VH5 among anti-HIV-1 mAbs, while non-HIV-1 specific mAbs preferentially used VH3 family genes, followed by VH4, VH1 and VH5 families in a pattern identical to Abs derived from healthy individuals. This observation suggests that the biased usage of Ig genes by anti-HIV-1 mAbs is driven by structural requirements of the virus antigens rather than by compensation to any depletion of VH3 B cells due to autoreactive mechanisms, according to the gp120 superantigen hypothesis

Biomorpher: interactive evolution for parametric design

Combining graph-based parametric design with metaheuristic solvers has to date focussed solely on performance based criteria and solving clearly defined objectives. In this paper, we outline a new method for combining a parametric modelling environment with an interactive Cluster-Orientated Genetic Algorithm (COGA). In addition to performance criteria, evolutionary design exploration can be guided through choice alone, with user motivation that cannot be easily defined. As well as numeric parameters forming a genotype, the evolution of whole parametric definitions is discussed through the use of genetic programming. Visualisation techniques that enable mixing small populations for interactive evolution with large populations for performance-based optimisation are discussed, with examples from both academia and industry showing a wide range of applications

Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: A centre randomised, cross-over, open-label study in the Netherlands

Objective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. Design: Centre randomised, open-label, crossover, 'real-life' study. Setting: 15 Dutch hospitals. Patients: Adult medical and post-surgical ICU patients with anticipated short-term (2-3 days) MV. Interventions: Patient cohorts were randomised to remifentanil-based regimen (n = 96) with propofol as required, for a maximum of 10 days, or to conventional regimens (n = 109) of propofol, midazolam or lorazepam combined with fentanyl or morphine. Measurements and main results: Outcomes were weaning time, duration of MV, ICU-LOS, sedation- and analgesia levels, intensivist/ICU nurse satisfaction, adverse events, mean arterial pressure, heart rate. Median duration of ventilation (MV) was 5.1 days with conventional treatment versus 3.9 days with remifentanil (NS). The remifentanil-based regimen reduced median weaning time by 18.9 h (P = 0.0001). Median ICU-LOS was 7.9 days versus 5.9 days, respectively (NS). However, the treatment effects on duration of MV and ICU stay were time-dependent: patients were almost twice as likely to be extubated (P = 0.018) and discharged from the ICU (P = 0.05) on day 1-3. Propofol doses were reduced by 20% (P = 0.05). Remifentanil also improved sedation-agitation scores (P < 0.0001) and intensivist/ICU nurse satisfaction (P < 0.0001). All other outcomes were comparable. Conclusions: In patients with an expected short-term duration of MV, remifentanil significantly improves sedation and agitation levels and reduces weaning time. This contributes to a shorter duration of MV and ICU-LOS

A qualitative exploration of the human resource policy implications of voluntary counselling and testing scale-up in Kenya: applying a model for policy analysis

Background: Kenya experienced rapid scale up of HIV testing and counselling services in government health services from 2001. We set out to examine the human resource policy implications of scaling up HIV testing and counselling in Kenya and to analyse the resultant policy against a recognised theoretical framework of health policy reform (policy analysis triangle). Methods: Qualitative methods were used to gain in-depth insights from policy makers who shaped scale up. This included 22 in-depth interviews with Voluntary Counselling and Testing (VCT) task force members, critical analysis of 53 sets of minutes and diary notes. We explore points of consensus and conflict amongst policymakers in Kenya and analyse this content to assess who favoured and resisted new policies, how scale up was achieved and the importance of the local context in which scale up occurred. Results: The scale up of VCT in Kenya had a number of human resource policy implications resulting from the introduction of lay counsellors and their authorisation to conduct rapid HIV testing using newly introduced rapid testing technologies. Our findings indicate that three key groups of actors were critical: laboratory professionals, counselling associations and the Ministry of Health. Strategic alliances between donors, NGOs and these three key groups underpinned the process. The process of reaching consensus required compromise and time commitment but was critical to a unified nationwide approach. Policies around quality assurance were integral in ensuring standardisation of content and approach. Conclusion: The introduction and scale up of new health service initiatives such as HIV voluntary counselling and testing necessitates changes to existing health systems and modification of entrenched interests around professional counselling and laboratory testing. Our methodological approach enabled exploration of complexities of scale up of HIV testing and counselling in Kenya. We argue that a better understanding of the diverse actors, the context and the process, is required to mitigate risks and maximise impact

New resources for functional analysis of omics data for the genus Aspergillus

<p>Abstract</p> <p>Background</p> <p>Detailed and comprehensive genome annotation can be considered a prerequisite for effective analysis and interpretation of omics data. As such, Gene Ontology (GO) annotation has become a well accepted framework for functional annotation. The genus <it>Aspergillus </it>comprises fungal species that are important model organisms, plant and human pathogens as well as industrial workhorses. However, GO annotation based on both computational predictions and extended manual curation has so far only been available for one of its species, namely <it>A. nidulans</it>.</p> <p>Results</p> <p>Based on protein homology, we mapped 97% of the 3,498 GO annotated <it>A. nidulans </it>genes to at least one of seven other <it>Aspergillus </it>species: <it>A. niger</it>, <it>A. fumigatus</it>, <it>A. flavus</it>, <it>A. clavatus</it>, <it>A. terreus</it>, <it>A. oryzae </it>and <it>Neosartorya fischeri</it>. GO annotation files compatible with diverse publicly available tools have been generated and deposited online. To further improve their accessibility, we developed a web application for GO enrichment analysis named FetGOat and integrated GO annotations for all <it>Aspergillus </it>species with public genome sequences. Both the annotation files and the web application FetGOat are accessible via the Broad Institute's website (<url>http://www.broadinstitute.org/fetgoat/index.html</url>). To demonstrate the value of those new resources for functional analysis of omics data for the genus <it>Aspergillus</it>, we performed two case studies analyzing microarray data recently published for <it>A. nidulans</it>, <it>A. niger </it>and <it>A. oryzae</it>.</p> <p>Conclusions</p> <p>We mapped <it>A. nidulans </it>GO annotation to seven other <it>Aspergilli</it>. By depositing the newly mapped GO annotation online as well as integrating it into the web tool FetGOat, we provide new, valuable and easily accessible resources for omics data analysis and interpretation for the genus <it>Aspergillus</it>. Furthermore, we have given a general example of how a well annotated genome can help improving GO annotation of related species to subsequently facilitate the interpretation of omics data.</p

Genes implicated in multiple sclerosis pathogenesis from consilience of genotyping and expression profiles in relapse and remission

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Although the pathogenesis of MS remains unknown, it is widely regarded as an autoimmune disease mediated by T-lymphocytes directed against myelin proteins and/or other oligodendrocyte epitopes.</p> <p>Methods</p> <p>In this study we investigated the gene expression profiles of peripheral blood cells from patients with RRMS during the relapse and the remission phases utilizing gene microarray technology. Dysregulated genes encoded in regions associated with MS susceptibility from genomic screens or previous trancriptomic studies were identified. The proximal promoter region polymorphisms of two genes were tested for association with disease and expression level.</p> <p>Results</p> <p>Distinct sets of dysregulated genes during the relapse and remission phases were identified including genes involved in apoptosis and inflammation. Three of these dysregulated genes have been previously implicated with MS susceptibility in genomic screens: TGFβ1, CD58 and DBC1. TGFβ1 has one common SNP in the proximal promoter: -508 T>C (rs1800469). Genotyping two Australian trio sets (total 620 families) found a trend for over-transmission of the T allele in MS in females (p < 0.13). Upregulation of CD58 and DBC1 in remission is consistent with their putative roles in promoting regulatory T cells and reducing cell proliferation, respectively. A fourth gene, ALOX5, is consistently found over-expressed in MS. Two common genetic variants were confirmed in the ALOX5 putatve promoter: -557 T>C (rs12762303) and a 6 bp tandem repeat polymorphism (GGGCGG) between position -147 and -176; but no evidence for transmission distortion found.</p> <p>Conclusion</p> <p>The dysregulation of these genes tags their metabolic pathways for further investigation for potential therapeutic intervention.</p

Characterization of regulatory T cells in urban newborns

© 2009 Ly et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer

Purpose: To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer. Methods: Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib. QT/QTc interval on the electrocardiograph (ECG) was measured in triplicate with a Holter 12-lead ECG at baseline and after 1 cycle of sorafenib. Heart rate (HR) and blood pressure (BP) were obtained in duplicate at baseline and after 1 and 4 cycles of sorafenib. Plasma pharmacokinetic data were obtained for sorafenib and its 3 main metabolites after 1 and 4 cycles of sorafenib. Results: LVEF (SD) mean change from baseline was -0.8 ($\pm$8.6) LVEF(%) after 2 cycles (n=31) and -1.2 $\pm$7.8) LVEF(%) after 4 cycles of sorafenib (n=24). The QT/QTc mean changes from baseline observed at maximum sorafenib concentrations ($t_{max}$) after 1 cycle (n=31) were small (QTcB: 4.2 ms; QTcF: 9.0 ms). Mean changes observed after 1 cycle in BP (n=31) and HR (n=30) at maximum sorafenib concentrations ($t_{max}$) were moderate (up to 11.7 mm Hg and -6.6 bpm, respectively). No correlation was found between the AUC and ($C_{max}$) of sorafenib and its main metabolites and any cardiovascular parameters. Conclusions: The effects of sorafenib on changes in QT/QTc interval on the ECG, LVEF, BP, and HR were modest and unlikely to be of clinical significance in the setting of advanced cancer treatment