A series of metal‐free organic dyes with a core phenoxazine chromophore have been synthesized and tested as sensitizers in dye‐sensitized solar cells. Overall conversion efficiencies of 6.03–7.40 % ...were reached under standard AM 1.5G illumination at a light intensity of 100 mW cm−2. A clear trend in electron lifetime could be seen; a dye with a furan‐conjugated linker showed a shorter lifetime relative to dyes with the acceptor group directly attached to the phenoxazine. The addition of an extra donor unit, which bore insulating alkoxyl chains, in the 7‐position of the phenoxazine could increase the lifetime even further and, together with additives in the electrolyte to raise the conduction band, an open circuit voltage of 800 mV could be achieved. From photoelectron spectroscopy and X‐ray absorption spectroscopy of the dyes adsorbed on TiO2 particles, it can be concluded that the excitation is mainly of cyano character (i.e., on average, the dye molecules are standing on, and pointing out, from the surface of TiO2 particles).
Make a donation: The structural modification of phenoxazine‐based sensitizers has a large influence on the electron lifetime, which in turn affects the overall performance of solar cells. Of the five dyes synthesized (see scheme), the best dye shows a solar energy‐to‐electricity conversion efficiency of 7.4 %, together with a high open‐circuit photovoltage of 800 mV.
Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of ...abacavir-reacting CD8+ T cells, which release IFNγ and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. These features are reminiscent of allo-reactivity. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele ('altered self-allele') and create the potential for robust T cell responses.
In the current work we characterize the uptake mechanism of two NickFect family members, NF51 and NF1, related to the biological activity of transfected plasmid DNA (pDNA). Both vectors condense pDNA ...into small negatively charged nanoparticles that transfect HeLa cells with equally high efficacy and the delivery is mediated by SCARA3 and SCARA5 receptors. NF1 condenses DNA into less homogeneous and less stable nanoparticles than NF51. NF51/pDNA nanoparticles enter the cells via macropinocytosis, while NF1/pDNA complexes use clathrin- or caveolae-mediated endocytosis and macropinocytosis. Analysis of separated endosomal compartments uncovered lysomotropic properties of NF51 that was also proven by cotransfection with chloroquine. In summary we characterize how radical modifications in peptides, such as introducing a kink in the structure of NF51 or including extra negative charge by phospho-tyrosine substitution in NF1, resulted in equally high efficacy for gene delivery, although this efficacy is achieved by using differential transfection pathways.
During the last two decades major changes of the benthic fauna have occurred in the northern Baltic Sea, the Gulf of Bothnia. The native amphipod, Monoporeia affinis, has shown a large-scale ...abundance decrease, while polychaetes, Marenzelleria spp. have invaded the system. Marenzelleria co-exist with the native fauna in the southern Baltic Sea, but in the north the pelagic production might be too low to allow co-existence. Thus, M. affinis might have been out-competed by Marenzelleria in the Gulf of Bothnia. This hypothesis was tested in a competition experiment with a high and a low fresh phytoplankton food supply. When exposed to high food supply both species showed stable or increased biomass over the four week test period. In low food supply, however, M. affinis was found to have a competitive advantage. The experimental data were also related to Baltic Sea monitoring data on primary production, sedimentation and invertebrate abundances. Data from the northern Baltic Sea show that the dominance in the benthic community by M. affinis was replaced by Marenzelleria around 2001. The amphipod decrease might be explained by a marked decrease in primary production during this period. Combining monitoring and experimental data suggests that the invasion of Marenzelleria did not cause the decrease of M. affinis in the northern Baltic Sea; it rather took advantage of the density gap that had occurred. A shift may thus have been established in the Bothnian Sea benthic community.
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•Monoporeia affinis is superior of Marenzelleria at low resources of high quality.•Monitoring data show that M. affinis is declined significantly from 1998 to 2001.•Marenzelleria used a density gap to increase its abundance in the Gulf of Bothnia.•The abundance of M. affinis and primary production are strongly correlated.
When semi-natural pastures are abandoned, specialized grassland species are lost as a consequence of succession. As a counter-measure, previously abandoned grasslands may be restored by clearing ...shrubs and trees and re-introducing grazing livestock. In order to examine the effects of this type of habitat restoration, we compared species richness of plants and of specialized plants thought to be dependent on continuous management and species richness and abundance of butterflies and red-listed butterflies in 12 sets of matched continuously managed, abandoned and restored grassland in southern Sweden. We found no differences in species richness or abundance between the three grassland types. There were, however, some negative effects of abandonment. The number of management-dependent plants decreased with increasing cover of trees and shrubs, and in restored sites species richness of all groups decreased with increasing cover of trees and shrubs before restoration. Also the present management significantly affected both butterflies and plants. Species richness of both groups increased with increasing vegetation height and differed between sites depending on the species of grazers, with negative effects of sheep compared to cattle or horses. Our study indicates that for grassland management to be efficient, the restoration actions should mainly be directed towards sites where the post-abandonment succession has not proceeded too far.
Objective To compare mortality in chronic kidney disease (CKD) stages 4 and 5 (estimated glomerular filtration rate <30 mL/min/1.73 m2), peritoneal dialysis, haemodialysis and transplanted patients. ...Design Population-based cohort study. Setting Swedish national healthcare system. Participants Swedish adult patients with CKD stages 4 and 5 (n=3040; mean age 66 years), peritoneal dialysis (n=725; 60 years), haemodialysis (n=1791; 62 years) and renal transplantation (n=606; 48 years) were identified in Stockholm County clinical quality registers for renal disease between 1999 and 2010. Five general population controls were matched to each patient by age, sex and index year. Exposure CKD status (stage 4 or 5/peritoneal dialysis/haemodialysis/transplanted). Primary outcome All-cause mortality was ascertained from the Swedish Causes of Death Register. Mortality HRs were estimated using Cox regression conditioned on age, sex, diabetes status, education level and index year. Results During 6553 person-years, 766 patients with CKD stages 4 and 5 died (deaths/100 person-years 12, 95% CI 11 to 13) compared with 186 deaths during 1113 person-years in peritoneal dialysis (17, 95% CI 15 to 19), 924 deaths during 3680 person-years in haemodialysis (25, 95% CI 23 to 27) and 53 deaths during 2935 person-years in transplanted patients (1.8, 95% CI 1.4 to 2.4). Against matched general population controls, the mortality HR was 3.6 (95% CI 3.2 to 4.0) for CKD, 5.6 (95% CI 3.5 to 8.9) for transplanted patients, 9.2 (95% CI 6.6 to 12.7) for peritoneal dialysis and 12.6 (95% CI 10.8 to 14.6) for haemodialysis. In direct comparison versus CKD, the mortality HR was 1.7 (95% CI 1.4 to 2.1) for peritoneal dialysis, 2.6 (95% CI 2.3 to 2.9) for haemodialysis and 0.5 (95% CI 0.3 to 0.7) for transplanted patients. Conclusions We did not find support for mortality in CKD to be similar to dialysis mortality. The patients with CKD stages 4 and 5 had considerably lower mortality risk than dialysis patients, and considerably higher risk than transplanted patients and matched general population controls.
To compare drug survival on adalimumab, etanercept and infliximab in patients with rheumatoid arthritis (RA).
Patients with RA (n=9139; 76% women; mean age 56 years) starting their first tumour ...necrosis factor (TNF) inhibitor between 2003 and 2011 were identified in the Swedish Biologics Register (ARTIS). Data were collected through 31 December 2011. Drug survival over up to 5 years of follow-up was compared overall and by period of treatment start (2003-2005/2006-2009; n=3168/4184) with adjustment for age, sex, education, period, health assessment questionnaire (HAQ), disease duration, concomitant disease modifying antirheumatic drug (DMARD) treatment and general frailty (using hospitalisation history as proxy).
During 20 198 person-years (mean/median 2.2/1.7 years) of follow-up, 3782 patients discontinued their first biological (19/100 person-years; 51% due to inefficacy, 36% due to adverse events). Compared with etanercept, infliximab (adjusted HR 1.63, 95% CI 1.51 to 1.77) and adalimumab initiators had higher discontinuation rates (1.26, 95% CI 1.16 to 1.37), and infliximab had a higher discontinuation rate than adalimumab (1.28, 95% CI 1.18 to 1.40). These findings were consistent across periods, but were modified by time for adalimumab versus etanercept (p<0.001; between-drug difference highest the 1st year in both periods). The discontinuation rate was higher for starters in 2006-2009 than 2003-2005 (adjusted HR 1.12, 95% CI 1.04 to 1.20). The composition of 1-year discontinuations also changed from 2003-2005 vs 2006-2009: adverse events decreased from 45% to 35%, while inefficacy increased from 43% to 53% (p<0.001).
Discontinuation rates were higher for infliximab compared with adalimumab and etanercept initiators, and for adalimumab versus etanercept during the 1st year. Discontinuation rates increased with calendar period, as did the percentage discontinuations due to inefficacy.
The hypothalamic orexin (hypocretin) neuropeptides are associated with the regulation of sleep and feeding, and disturbances in orexinergic neurotransmission lead to a narcoleptic phenotype. ...Histamine has also been shown to play a role in the regulation of sleep and feeding. Therefore, we studied the relationship between the orexin and histamine systems of the CNS using electrophysiology, immunocytochemistry, and the reverse transcriptase (RT)-PCR method. Both orexin-A and orexin-B depolarized the histaminergic tuberomammillary neurons and increased their firing rate via an action on postsynaptic receptors. The depolarization was associated with a small decrease in input resistance and was likely caused by activation of both the electrogenic Na(+)/Ca(2+) exchanger and a Ca(2+) current. In a single-cell RT-PCR study using primers for the two orexin receptors, we found that most tuberomammillary neurons express both receptors and that the expression of the orexin-2 receptor is stronger than that of the orexin-1 receptor. Immunocytochemical studies show that the histamine and orexin neurons are often located very close to each other. The contacts between these two types of neurons seem to be reciprocal, because the orexin neurons are heavily innervated by histaminergic axons. These results suggest a functional connection between the two populations of hypothalamic neurons and that they may cooperate in the regulation of rapid-eye-movement sleep and feeding.
Adverse drug reactions are one of the leading causes of morbidity and mortality in health care worldwide. Human leukocyte antigen (HLA) alleles have been strongly associated with drug ...hypersensitivities, and the causative drugs have been shown to stimulate specific T cells at the sites of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context of small molecule drugs are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as a model system, this study examines structural similarities of HLA presented peptides recognized by drug-specific TCRs. Using the crystal structure of HLA-B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV SPT5a 976-984, peptide side chains exhibiting flexibility and solvent exposure were identified as potential drug-specific T cell recognition motifs. Viral sequences with structural motifs similar to the immunogenic self peptide were identified. Abacavir-specific T cell clones were used to determine if virus peptides presented in the context of abacavir stimulate T cell responsiveness. An abacavir-specific T cell clone was stimulated by VTQQAQVRL, corresponding to HSV1/2 230-238, in the context of HLA-B*57:01. These data suggest the T cell polyclonal response to abacavir consists of multiple subsets, including T cells that recognize self peptide/HLA-B*57:01 complexes and crossreact with viral peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues.
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