Alternative antibody for the detection of CA19-9 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access (R) GI Monitor assay on the UniCel (R) Dxl 800 Immunoassay System

Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access(R) GI Monitor assay (Beckman Coulter) was evaluated on the UniCel(R) Dxl 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access' GI Monitor and Elecsys CA19-9 (R = 0.959, slope = 1.004, intercept +0.17). GI Monitor serum levels were low in healthy individuals (n = 267, median = 6.0 kU/L, 95th percentile = 23.1 kU/L), higher in individuals with various benign diseases (n = 550, medians = 5.8-13.4 kU/L, 95th percentiles = 30.1-195.5 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 8.4-233.8 kU/L, 95th percentiles = 53.7-13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer {[}area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access(R) GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers

Near-field probing of strong light-matter coupling in single IR antennae

Quantum well intersubband polaritons are traditionally studied in large scale systems, over many wavelengths in size. In this presentation, we demonstrate that it is possible to detect and investigate intersubband polaritons in a single subwavelength nanoantenna in the IR frequency range. We observe polariton formation using a scattering-type near-field microscope and nano-FTIR spectroscopy. We will discuss near-field spectroscopic signatures of plasmonic antennae with and without coupling to the intersubband transition in quantum wells located underneath the antenna. Evanescent field amplitude spectra recorded on the antenna surface show a mode anti-crossing behavior in the strong coupling case. We also observe a corresponding strong-coupling signature in the phase of the detected field. We anticipate that this near-field approach will enable explorations of strong and ultrastrong light-matter coupling in the single nanoantenna regime, including investigations of the elusive effect of ISB polariton condensation

A stitch in time: Efficient computation of genomic DNA melting bubbles

Background: It is of biological interest to make genome-wide predictions of the locations of DNA melting bubbles using statistical mechanics models. Computationally, this poses the challenge that a generic search through all combinations of bubble starts and ends is quadratic. Results: An efficient algorithm is described, which shows that the time complexity of the task is O(NlogN) rather than quadratic. The algorithm exploits that bubble lengths may be limited, but without a prior assumption of a maximal bubble length. No approximations, such as windowing, have been introduced to reduce the time complexity. More than just finding the bubbles, the algorithm produces a stitch profile, which is a probabilistic graphical model of bubbles and helical regions. The algorithm applies a probability peak finding method based on a hierarchical analysis of the energy barriers in the Poland-Scheraga model. Conclusions: Exact and fast computation of genomic stitch profiles is thus feasible. Sequences of several megabases have been computed, only limited by computer memory. Possible applications are the genome-wide comparisons of bubbles with promotors, TSS, viral integration sites, and other melting-related regions.Comment: 16 pages, 10 figure

Co3O4 Nanocrystals on Graphene as a Synergistic Catalyst for Oxygen Reduction Reaction

Catalysts for oxygen reduction and evolution reactions are at the heart of key renewable energy technologies including fuel cells and water splitting. Despite tremendous efforts, developing oxygen electrode catalysts with high activity at low costs remains a grand challenge. Here, we report a hybrid material of Co3O4 nanocrystals grown on reduced graphene oxide (GO) as a high-performance bi-functional catalyst for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). While Co3O4 or graphene oxide alone has little catalytic activity, their hybrid exhibits an unexpected, surprisingly high ORR activity that is further enhanced by nitrogen-doping of graphene. The Co3O4/N-doped graphene hybrid exhibits similar catalytic activity but superior stability to Pt in alkaline solutions. The same hybrid is also highly active for OER, making it a high performance non-precious metal based bi-catalyst for both ORR and OER. The unusual catalytic activity arises from synergetic chemical coupling effects between Co3O4 and graphene.Comment: published in Nature Material

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

Identification of new transitions and mass assignments of levels in 143−153^{143-153}Pr

The previously reported levels assigned to 151,152,153Pr have recently been called into question regarding their mass assignment. The above questioned level assignments are clarified by measuring g-transitions tagged with A and Z in an in-beam experiment in addition to the measurements from 252Cf spontaneous fission (SF) and establish new spectroscopic information from $N=84$ to $N=94$ in the Pr isotopic chain. The isotopic chain 143-153Pr has been studied from the spontaneous fission of 252Cf by using Gammasphere and also from the measurement of the prompt g-rays in coincidence with isotopically-identified fission fragments using VAMOS++ and EXOGAM at GANIL. The latter were produced using 238U beams on a 9Be target at energies around the Coulomb barrier. The g-g-g-g data from 252Cf (SF) and those from the GANIL in-beam A- and Z-gated spectra were combined to unambiguously assign the various transitions and levels in 151,152,153Pr and other isotopes. New transitions and bands in 145,147,148,149,150Pr were identified by using g-g-g and g-g-g-g coincidences and A and Z gated g-g spectra. The transitions and levels previously assigned to 151,153Pr have been confirmed by the (A,Z) gated spectra. The transitions previously assigned to 152Pr are now assigned to 151Pr on the basis of the (A,Z) gated spectra. Two new bands with 20 new transitions in 152Pr and one new band with 7 new transitions in 153Pr are identified from the g-g-g-g coincidence spectra and the (A,Z) gated spectrum. In addition, new g-rays are also reported in 143-146Pr. New levels of 145,147-153Pr have been established, reliable mass assignments of the levels in 151,152,153Pr have been reported and new transitions have been identified in 143-146Pr showing the new avenues that are opened by combining the two experimental approaches.Comment: Accepted in Phys. Rev.

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour

PIM-1 as a Multifunctional Framework to Enable High-Performance Solid-State Lithium-Sulfur Batteries

Poly(ethylene oxide) (PEO) is a promising solid electrolyte material for solid-state lithium–sulfur (Li–S) batteries, but low intrinsic ionic conductivity, poor mechanical properties, and failure to hinder the polysulfide shuttle effect limits its application. Herein, a polymer of intrinsic microporosity (PIM) is synthesized and applied as an organic framework to comprehensively enhance the performance of PEO by forming a composite electrolyte (PEO-PIM). The unique structure of PIM-1 not only enhances the mechanical strength and hardness over the PEO electrolyte by an order of magnitude, increasing stability toward the metallic lithium anode but also increases its ionic conductivity by lowering the degree of crystallinity. Furthermore, the PIM-1 is shown to effectively trap lithium polysulfide species to mitigate against the detrimental polysulfide shuttle effect, as electrophilic 1,4-dicyanooxanthrene functional groups possess higher binding energy to polysulfides. Benefiting from these properties, the use of PEO-PIM composite electrolyte has achieved greatly improved rate performance, long-cycling stability, and excellent safety features for solid-state Li-S batteries. This methodology offers a new direction for the optimization of solid polymer electrolytes

Direct entropy determination and application to artificial spin ice

From thermodynamic origins, the concept of entropy has expanded to a range of statistical measures of uncertainty, which may still be thermodynamically significant. However, laboratory measurements of entropy continue to rely on direct measurements of heat. New technologies that can map out myriads of microscopic degrees of freedom suggest direct determination of configurational entropy by counting in systems where it is thermodynamically inaccessible, such as granular and colloidal materials, proteins and lithographically fabricated nanometre-scale arrays. Here, we demonstrate a conditional-probability technique to calculate entropy densities of translation-invariant states on lattices using limited configuration data on small clusters, and apply it to arrays of interacting nanometre-scale magnetic islands (artificial spin ice). Models for statistically disordered systems can be assessed by applying the method to relative entropy densities. For artificial spin ice, this analysis shows that nearest-neighbour correlations drive longer-range ones.Comment: 10 page

Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of >0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes