Imaging angiogenesis in atherosclerosis in large arteries with 68Ga-NODAGA-RGD PET/CT: relationship with clinical atherosclerotic cardiovascular disease.

Integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of <sup>68</sup> Ga-NODAGA-RGD, a specific α <sub>v</sub> β <sub>3</sub> integrin ligand for PET. The data of 44 patients who underwent <sup>68</sup> Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann-Whitney U test, Pearson correlation and Spearman correlation. <sup>68</sup> Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03-2.55] vs. 1.81 [1.56-1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04). <sup>68</sup> Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis

Applications of Nanoscale Materials in the Fields of Electrochemistry and Photoelectrochemistry

We have illustrated the important role played by the nanoscale materials in three-up-to-date energy topics

Assessing the role of EO in biodiversity monitoring: options for integrating in-situ observations with EO within the context of the EBONE concept

The European Biodiversity Observation Network (EBONE) is a European contribution on terrestrial monitoring to GEO BON, the Group on Earth Observations Biodiversity Observation Network. EBONE’s aims are to develop a system of biodiversity observation at regional, national and European levels by assessing existing approaches in terms of their validity and applicability starting in Europe, then expanding to regions in Africa. The objective of EBONE is to deliver: 1. A sound scientific basis for the production of statistical estimates of stock and change of key indicators; 2. The development of a system for estimating past changes and forecasting and testing policy options and management strategies for threatened ecosystems and species; 3. A proposal for a cost-effective biodiversity monitoring system. There is a consensus that Earth Observation (EO) has a role to play in monitoring biodiversity. With its capacity to observe detailed spatial patterns and variability across large areas at regular intervals, our instinct suggests that EO could deliver the type of spatial and temporal coverage that is beyond reach with in-situ efforts. Furthermore, when considering the emerging networks of in-situ observations, the prospect of enhancing the quality of the information whilst reducing cost through integration is compelling. This report gives a realistic assessment of the role of EO in biodiversity monitoring and the options for integrating in-situ observations with EO within the context of the EBONE concept (cfr. EBONE-ID1.4). The assessment is mainly based on a set of targeted pilot studies. Building on this assessment, the report then presents a series of recommendations on the best options for using EO in an effective, consistent and sustainable biodiversity monitoring scheme. The issues that we faced were many: 1. Integration can be interpreted in different ways. One possible interpretation is: the combined use of independent data sets to deliver a different but improved data set; another is: the use of one data set to complement another dataset. 2. The targeted improvement will vary with stakeholder group: some will seek for more efficiency, others for more reliable estimates (accuracy and/or precision); others for more detail in space and/or time or more of everything. 3. Integration requires a link between the datasets (EO and in-situ). The strength of the link between reflected electromagnetic radiation and the habitats and their biodiversity observed in-situ is function of many variables, for example: the spatial scale of the observations; timing of the observations; the adopted nomenclature for classification; the complexity of the landscape in terms of composition, spatial structure and the physical environment; the habitat and land cover types under consideration. 4. The type of the EO data available varies (function of e.g. budget, size and location of region, cloudiness, national and/or international investment in airborne campaigns or space technology) which determines its capability to deliver the required output. EO and in-situ could be combined in different ways, depending on the type of integration we wanted to achieve and the targeted improvement. We aimed for an improvement in accuracy (i.e. the reduction in error of our indicator estimate calculated for an environmental zone). Furthermore, EO would also provide the spatial patterns for correlated in-situ data. EBONE in its initial development, focused on three main indicators covering: (i) the extent and change of habitats of European interest in the context of a general habitat assessment; (ii) abundance and distribution of selected species (birds, butterflies and plants); and (iii) fragmentation of natural and semi-natural areas. For habitat extent, we decided that it did not matter how in-situ was integrated with EO as long as we could demonstrate that acceptable accuracies could be achieved and the precision could consistently be improved. The nomenclature used to map habitats in-situ was the General Habitat Classification. We considered the following options where the EO and in-situ play different roles: using in-situ samples to re-calibrate a habitat map independently derived from EO; improving the accuracy of in-situ sampled habitat statistics, by post-stratification with correlated EO data; and using in-situ samples to train the classification of EO data into habitat types where the EO data delivers full coverage or a larger number of samples. For some of the above cases we also considered the impact that the sampling strategy employed to deliver the samples would have on the accuracy and precision achieved. Restricted access to European wide species data prevented work on the indicator ‘abundance and distribution of species’. With respect to the indicator ‘fragmentation’, we investigated ways of delivering EO derived measures of habitat patterns that are meaningful to sampled in-situ observations

The Development of Peptide-Based Tools for the Analysis of Angiogenesis

SummaryLimitations to the application of molecularly targeted cancer therapies are the inability to accurately match patient with effective treatment and the absence of a prompt readout of posttreatment response. Noninvasive agents that rapidly report vascular endothelial growth factor (VEGF) levels using positron emission tomography (PET) have the potential to enhance anti-angiogenesis therapies. Using phage display, two distinct classes of peptides were identified that bind to VEGF with nanomolar affinity and high selectivity. Co-crystal structures of these different peptide classes demonstrate that both bind to the receptor-binding region of VEGF. 18F-radiolabelling of these peptides facilitated the acquisition of PET images of tumor VEGF levels in a HM7 xenograph model. The images obtained from one 59-residue probe, 18F-Z-3B, 2 hr postinjection are comparable to those obtained with anti-VEGF antibody B20 72 hr postinjection. Furthermore, VEGF levels in growing SKOV3 tumors were followed using 18F-Z-3B as a PET probe with VEGF levels increasing with tumor size

Efficacy of Continuous Interleukin 1 Blockade in Mevalonate Kinase Deficiency: A Multicenter Retrospective Study in 13 Adult Patients and Literature Review

OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD). METHODS: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7). RESULTS: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively. CONCLUSION: These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment

PLR (Plastic Lithium Rechargeable) Batteries Using Nanoscale Materials: A Convenient Electrical Energy Power for the Future?

This communication describes the synthesis of: (i) non toxic and low cost nanocrystalline electrode materials which can be advantageously prepared at low temperature; (ii) highly conductive electrolyte membranes formed by the nano-encapsulation within a poly (acrylonitrile)-based polymer matrix of a solution of LiPF6 in organic solvants. The performances of rechargeable PLR (Plastic Lithium Rechargeable) batteries using the above mentioned components are presented

Dynamic Measurements of Membrane Insertion Potential of Synthetic Cell Penetrating Peptides

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/la403370p.Cell penetrating peptides (CPPs) have been established as excellent candidates for mediating drug delivery into cells. When designing synthetic CPPs for drug delivery applications, it is important to understand their ability to penetrate the cell membrane. In this paper, anionic or zwitterionic phospholipid monolayers at the air-water interface are used as model cell membranes to monitor the membrane insertion potential of synthetic CPPs. The insertion potential of CPPs having different cationic and hydrophobic amino acids were recorded using a Langmuir monolayer approach that records peptide adsorption to model membranes. Fluorescence microscopy was used to visualize alterations in phospholipid packing due to peptide insertion. All CPPs had the highest penetration potential in the presence of anionic phospholipids. In addition, two of three amphiphilic CPPs inserted into zwitterionic phospholipids, but none of the hydrophilic CPPs did. All the CPPs studied induced disruptions in phospholipid packing and domain morphology, which were most pronounced for amphiphilic CPPs. Overall, small changes to amino acids and peptide sequences resulted in dramatically different insertion potentials and membrane reorganization. Designers of synthetic CPPs for efficient intracellular drug delivery should consider small nuances in CPP electrostatic and hydrophobic properties

Cross-shell states in 15^{15}C: a test for p-sd interactions

The low-lying structure of $^{15}$C has been investigated via the neutron-removal $^{16}$C$(d,t)$ reaction. Along with bound neutron sd-shell hole states, unbound p-shell hole states have been firmly confirmed. The excitation energies and the deduced spectroscopic factors of the cross-shell states are an important measure of the $[(p)^{-1}(sd)^{2}]$ neutron configurations in $^{15}$C. Our results show a very good agreement with shell-model calculations using the SFO-tls interaction for $^{15}$C. However, a modification of the $p$-$sd$ and $sd$-$sd$ monopole terms was applied in order to reproduce the $N=9$ isotone $^{17}$O. In addition, the excitation energies and spectroscopic factors have been compared to the first calculations of $^{15}$C with the $ab~ initio$ self-consistent Green's function method employing the NNLO$_{sat}$ interaction. The results show the sensitivity to the size of the $N=8$ shell gap and highlight the need of going beyond the current truncation scheme in the theory

Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors

Intruder configurations in 29^{29}Ne at the transition into the island of inversion: Detailed structure study of 28^{28}Ne

Detailed $\gamma$-ray spectroscopy of the exotic neon isotope $^{28}$Ne has been performed for the first time using the one-neutron removal reaction from $^{29}$Ne on a liquid hydrogen target at 240~MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for $^{28}$Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder $p$-wave strength providing evidence of the breakdown of the $N=20$ and $N=28$ shell gaps. Only a weak, possible $f$-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large $p$-wave and small $f$-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain