Excited states of linear polyenes

We present density matrix renormalisation group calculations of the Pariser- Parr-Pople-Peierls model of linear polyenes within the adiabatic approximation. We calculate the vertical and relaxed transition energies, and relaxed geometries for various excitations on long chains. The triplet (3Bu+) and even- parity singlet (2Ag+) states have a 2-soliton and 4-soliton form, respectively, both with large relaxation energies. The dipole-allowed (1Bu-) state forms an exciton-polaron and has a very small relaxation energy. The relaxed energy of the 2Ag+ state lies below that of the 1Bu- state. We observe an attraction between the soliton-antisoliton pairs in the 2Ag+ state. The calculated excitation energies agree well with the observed values for polyene oligomers; the agreement with polyacetylene thin films is less good, and we comment on the possible sources of the discrepencies. The photoinduced absorption is interpreted. The spin-spin correlation function shows that the unpaired spins coincide with the geometrical soliton positions. We study the roles of electron-electron interactions and electron-lattice coupling in determining the excitation energies and soliton structures. The electronic interactions play the key role in determining the ground state dimerisation and the excited state transition energies.Comment: LaTeX, 15 pages, 9 figure

Female resistance to pneumonia identifies lung macrophage nitric oxide synthase-3 as a therapeutic target

To identify new approaches to enhance innate immunity to bacterial pneumonia, we investigated the natural experiment of gender differences in resistance to infections. Female and estrogen-treated male mice show greater resistance to pneumococcal pneumonia, seen as greater bacterial clearance, diminished lung inflammation, and better survival. In vitro, lung macrophages from female mice and humans show better killing of ingested bacteria. Inhibitors and genetically altered mice identify a critical role for estrogen-mediated activation of lung macrophage nitric oxide synthase-3 (NOS3). Epidemiologic data show decreased hospitalization for pneumonia in women receiving estrogen or statins (known to activate NOS3). Pharmacologic targeting of NOS3 with statins or another small-molecule compound (AVE3085) enhanced macrophage bacterial killing, improved bacterial clearance, and increased host survival in both primary and secondary (post-influenza) pneumonia. The data identify a novel mechanism for host defense via NOS3 and suggest a potential therapeutic strategy to reduce secondary bacterial pneumonia after influenza. DOI: http://dx.doi.org/10.7554/eLife.03711.00

The evolution and preservation potential of englacial eskers: An example from Breiðamerkurjökull, SE Iceland

Directly observing glacial drainage systems (englacial and subglacial) is challenging. The distribution, morphology and internal structure of eskers can provide valuable information about the glacial drainage system and meltwater processes. This work presents the annual evolution (meltout) and internal structure of an esker emerging from the Breiðamerkurjökull ice margin, southeast Iceland. Changes in esker morphology have been repeatedly mapped over a 1‐year period using high temporal and spatial resolution data acquired by an uncrewed aerial vehicle (UAV). The internal architecture of the esker was investigated using ground‐penetrating radar (GPR) surveys. These data are used to identify the dominant processes driving the formation of this englacial esker and to evaluate the preservation potential. The englacial esker was up to 2.6 m thick and ice‐cored. A large moulin upglacier of the esker, which evolved into an englacial conduit, supplied meltwater to the englacial channel. Upglacier dipping debris‐filled basal hydrofractures, formed by pressurised subglacial meltwater rising up the retrograde bed slope, likely supplied sediment to the englacial conduit. Over the 1‐year period of observation the crest morphology evolved from flat‐ to sharp‐crested and the esker footprint increased by a factor of 5.7 in response to post‐depositional processes. The findings presented here indicate that englacial eskers may have low preservation potential due to post‐depositional reworking such as slumping through ice‐core meltout and erosion by later meltwater flow. As englacial eskers may not be preserved in the landscape, they could represent important glacial drainage system components that are not currently captured in palaeo‐ice sheet reconstructions. This work highlights the value of creating a time series of high‐temporal resolution data to quantify morphological evolution and improve glacial process‐form models

Effect of continuous nutrient enrichment on microalgae colonizing hard substrates

In order to understand the effect of changing nutrient conditions on benthic microalgae on hard substrates, in-situ experiments with artificial substrates were conducted in Kiel Fjord, Western Baltic Sea. As an extension of previous investigations, we used artificial substrates without silicate and thus were able to supply nutrient media with different Si:N ratios to porous substrates, from where they trickled out continuously. The biofilm developing on these substrates showed a significant increase in biovolume due to N + P enrichment, while Si alone had only minor effects. The stoichiometric composition of the biomass indicated nitrogen limitation during most of the year. The C:N ratios were lowered by the N + P addition. The algae were dominated by diatoms in most cases, but rhodophytes and chlorophytes also became important. The nutrient treatment affected the taxonomic composition mostly at the species level. The significance of the results with regard to coastal eutrophication is discussed

Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease-causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.We are indebted to all families for participating in this study. We would like to acknowledge Dr. Natasha Laidlew, who initially suggested the diagnosis in one of the cases and provided important phenotypic information, and Dr. María-Luisa Martínez-Fernández for the critical management of biosamples in ECEMC Program of Spain. Financial assistance was received in support of the study by grants from the German Federal Ministry of Education and Research (BMBF) (GeNeRARe, FKZ: 01GM1519D) to M. Z. and from the Institute of Health Carlos III: Convenio ISCIII-ASEREMAC, and Fundación 1000 sobre Defectos Congénitos, of Spain to E. B.-S. and I. R. G.S

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth

Screening a phage-display single-chain antibody library for binding to the breast cancer cell line PM-1 an antibody, scFv173, recognising activated leukocyte cell adhesion molecule (ALCAM, CD166) was isolated and its binding profile was characterized. Positive ALCAM immunohistochemical staining of frozen human tumour sections was observed. No ALCAM staining was observed in the majority of tested normal human tissues (nine of ten). Flow cytometry analyses revealed binding to 22 of 26 cancer cell lines of various origins and no binding to normal blood and bone marrow cells. Antibody binding inhibited invasion of the breast cancer cell line MDA-MB-231 by 50% in an in vitro Matrigel-coated membrane invasion assay. Reduced growth of tumours in nude mice was observed in an in vivo model in which the mice were injected subcutaneously with colorectal carcinoma HCT 116 cells and treated with scFv173 when compared to control. In summary, we have characterized a novel fully human scFv antibody recognising ALCAM on cancer cells and in tumour tissues that reduces cancer cell invasion and tumour growth in accordance with the hypothesised role for ALCAM in cell growth and migration control

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age