Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) - Pluronic (R) F127 copolymers for controlled protein release

Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez (R) AN, GZ) and Pluronic (R) F127 (PF127) copolymers (GZ-PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol-gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.

Automated tumour annotation and analysis for molecular pathology using TissueMark (R)

Objective: Molecular pathology relies on identifying anomalies using PCR or analysis of DNA/RNA. This is important in solid tumours where molecular stratification of patients define targeted treatment. These molecular biomarkers rely on examination of tumour, annotation for possible macro dissection/tumour cell enrichment and the estimation of % tumour. Manually marking up tumour is error prone. Method: We have developed a method for automated tumour mark-up and % cell calculations using image analysis called TissueMark® based on texture analysis for lung, colorectal and breast (cases=245, 100, 100 respectively). Pathologists marked slides for tumour and reviewed the automated analysis. A subset of slides was manually counted for tumour cells to provide a benchmark for automated image analysis. Results: There was a strong concordance between pathological and automated mark-up (100 % acceptance rate for macro-dissection). We also showed a strong concordance between manually/automatic drawn boundaries (median exclusion/inclusion error of 91.70 %/89 %). EGFR mutation analysis was precisely the same for manual and automated annotation-based macrodissection. The annotation accuracy rates in breast and colorectal cancer were 83 and 80 % respectively. Finally, region-based estimations of tumour percentage using image analysis showed significant correlation with actual cell counts. Conclusion: Image analysis can be used for macro-dissection to (i) annotate tissue for tumour and (ii) estimate the % tumour cells and represents an approach to standardising/improving molecular diagnostics.

Genomic lesions associated with a different clinical outcome in diffuse large B-Cell lymphoma treated with R-CHOP-21

Despite recent therapeutic improvements, the clinical course of diffuse large B-cell lymphoma (DLBCL) still differs considerably among patients. We conducted this retrospective multi-centre study to evaluate the impact of genomic aberrations detected using a high-density genome wide-single nucleotide polymorphism-based array on clinical outcome in a population of DLBCL patients treated with R-CHOP-21 (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21_d). 166 DNA samples were analysed using the GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their impact on the clinical course of 124 patients treated with R-CHOP-21. Unsupervised clustering was performed to identify genetically related subgroups of patients with different clinical outcomes. Twenty recurrent genetic lesions showed an impact on the clinical course. Loss of genomic material at 8p23.1 showed the strongest statistical significance and was associated with additional aberrations, such as 17p- and 15q-. Unsupervised clustering identified five DLBCL clusters with distinct genetic profiles, clinical characteristics and outcomes. Genetic features and clusters, associated with a different outcome in patients treated with R-CHOP, have been identified by arrayCGH.

MarcoPolo-R near earth asteroid sample return mission

MarcoPolo-R is a sample return mission to a primitive Near-Earth Asteroid (NEA) proposed in collaboration with NASA. It will rendezvous with a primitive NEA, scientifically characterize it at multiple scales,and return a unique sample to Earth unaltered by the atmospheric entry process or terrestrial weathering. MarcoPolo-R will return bulk samples (up to 2 kg) from an organic-rich binary asteroid to Earth for laboratory analyses, allowing us to: explore the origin of planetary materials and initial stages of habitable planet formation; identify and characterize the organics and volatiles in a primitive asteroid; understand the unique geomorphology, dynamics and evolution of a binaryNEA. This project is based on the previous Marco Polo mission study,which was selected for the Assessment Phase of the first round of Cosmic Vision. Its scientific rationale was highly ranked by ESA committees andit was not selected only because the estimated cost was higher than theallotted amount for an M class mission. The cost of Marco Polo-R will be reduced to within the ESA medium mission budget by collaboration withAPL (John Hopkins University) and JPL in the NASA program for coordination with ESA's Cosmic Vision Call. The baseline target is a binary asteroid (175706) 1996 FG3, which offers a very efficient operational and technical mission profile. A binary target also providesenhanced science return. The choice of this target will allow newinvestigations to be performed more easily than at a single object, andalso enables investigations of the fascinating geology and geophysics ofasteroids that are impossible at a single object. Several launch windows have been identified in the time-span 2020-2024. A number of otherpossible primitive single targets of high scientific interest have beenidentified covering a wide range of possible launch dates. The baselinemission scenario of Marco Polo-R to 1996 FG3 is as follows: a singleprimary spacecraft provided by ESA, carrying the Earth Re-entry Capsule, sample acquisition and transfer system provided by NASA, will be launched by a Soyuz-Fregat rocket from Kourou into GTO and using two space segment stages. Two similar missions with two launch windows, in 2021 and 2022 and for both sample return in 2029 (with mission durationof 7 and 8 years), have been defined. Earlier or later launches, in 2020 or 2024, also offer good opportunities. All manoeuvres are carried out by a chemical propulsion system. MarcoPolo-R takes advantage of three industrial studies completed as part of the previous Marco Polo mission (see ESA/SRE (2009)3, Marco Polo Yellow Book) and of the expertise of the consortium led by Dr. A.F. Cheng (PI of the NASA NEAR Shoemaker mission) of the JHU-APL, including JPL, NASA ARC, NASA LaRC, and MIT.

Double ionization in R-matrix theory using a two-electron outer region

We have developed a two-electron outer region for use within R-matrix theory to describe double ionisation processes. The capability of this method is demonstrated for single-photon double ionisation of He in the photon energy region between 80 eV to 180 eV. The cross sections are in agreement with established data. The extended RMT method also provides information on higher-order processes, as demonstrated by the identification of signatures for sequential double ionisation processes involving an intermediate He⁺ state with n=2.