Solar and Reactor Neutrinos: Upcoming Experiments and Future Projects

Sub-MeV solar neutrino experiments and long-baseline reactor oscillation experiments toe the cutting edge of neutrino research. The upcoming experiments KamLAND and BOREXINO, currently in their startup and final construction phase respectively, will provide essential information on neutrino properties as well as on solar physics. Future projects, at present under development, will measure the primary solar neutrino fluxes via electron scattering and neutrino capture in real time. High precision data for lepton mixing as well as for stellar evolution theory will become available in the future. This paper aims to give an overview of the upcoming experiments and of the projects under development.Comment: 11 pages, 14 figures, LATEX (espcrc2.sty). Contribution to the proceedings of "TAUP2001 - Topics in Astroparticle and Underground Physics", LNGS, Italy (September 8-12, 2001

Thiol-gelatin-norbornene bioink for laser‐based high‐definition bioprinting

Two-photon polymerization (2PP) is a lithography-based 3D printing method allowing the fabrication of 3D structures with sub-micrometer resolution. This work focuses on the characterization of gelatin-norbornene (Gel-NB) bioinks which enables the embedding of cells via 2PP. The high reactivity of the thiol-ene system allows 2PP processing of cell-containing materials at remarkably high scanning speeds (1000 mm s(-1)) placing this technology in the domain of bioprinting. Atomic force microscopy results demonstrate that the indentation moduli of the produced hydrogel constructs can be adjusted in the 0.2-0.7 kPa range by controlling the 2PP processing parameters. Using this approach gradient 3D constructs are produced and the morphology of the embedded cells is observed in the course of 3 weeks. Furthermore, it is possible to tune the enzymatic degradation of the crosslinked bioink by varying the applied laser power. The 3D printed Gel-NB hydrogel constructs show exceptional biocompatibility, supported cell adhesion, and migration. Furthermore, cells maintain their proliferation capacity demonstrated by Ki-67 immunostaining. Moreover, the results demonstrate that direct embedding of cells provides uniform distribution and high cell loading independently of the pore size of the scaffold. The investigated photosensitive bioink enables high-definition bioprinting of well-defined constructs for long-term cell culture studies

Impact of hydrogel stiffness on differentiation of human adipose-derived stem cell microspheroids

Hydrogels represent an attractive material platform for realization of three-dimensional (3D) tissue-engineered constructs, as they have tunable mechanical properties, are compatible with different types of cells, and resemble elements found in natural extracellular matrices. So far, numerous hydrogel-cartilage/bone tissue engineering (TE)-related studies were performed by utilizing a single cell encapsulation approach. Although multicellular spheroid cultures exhibit advantageous properties for cartilage or bone TE, the chondrogenic or osteogenic differentiation potential of stem cell microspheroids within hydrogels has not been investigated much. This study explores, for the first time, how stiffness of gelatin-based hydrogels (having a storage modulus of 538, 3584, or 7263 Pa) affects proliferation and differentiation of microspheroids formed from telomerase-immortalized human adipose-derived stem cells (hASC/hTERT). Confocal microscopy indicates that all tested hydrogels supported cell viability during their 3- to 5-week culture period in the control, chondrogenic, or osteogenic medium. Although in the softer hydrogels cells from neighboring microspheroids started outgrowing and interconnecting within a few days, their protrusion was slower or limited in stiffer hydrogels or those cultured in chondrogenic medium, respectively. High expressions of chondrogenic markers (SOX9, ACAN, COL2A1), detected in all tested hydrogels, proved that the chondrogenic differentiation of hASC/hTERT microspheroids was very successful, especially in the two softer hydrogels, where superior cartilage-specific properties were confirmed by Alcian blue staining. These chondrogenically induced samples also expressed COL10A1, a marker of chondrocyte hypertrophy. Interestingly, the hydrogel itself (with no differentiation medium) showed a slight chondrogenic induction. Regardless of the hydrogel stiffness, in the samples stimulated with osteogenic medium, the expression of selected markers RUNX2, BGLAP, ALPL, and COL1A1 was not conclusive. Nevertheless, the von Kossa staining confirmed the presence of calcium deposits in osteogenically stimulated samples in the two softer hydrogels, suggesting that these also favor osteogenesis. This observation was also confirmed by Alizarin red quantification assay, with which higher amounts of calcium were detected in the osteogenically induced hydrogels than in their controls. The presented data indicate that the encapsulation of adipose-derived stem cell microspheroids in gelatin-based hydrogels show promising potential for future applications in cartilage or bone TE. Impact Statement Osteochondral defects represent one of the leading causes of disability in the world. Although numerous tissue engineering (TE) approaches have shown success in cartilage and bone tissue regeneration, achieving native-like characteristics of these tissues remains challenging. This study demonstrates that in the presence of a corresponding differentiation medium, gelatin-based hydrogels support moderate osteogenic and excellent chondrogenic differentiation of photo-encapsulated human adipose-derived stem cell microspheroids, the extent of which depends on hydrogel stiffness. Because photosensitive hydrogels are a convenient material platform for creating stiffness gradients in three dimensions, the presented microspheroid-hydrogel encapsulation strategy holds promise for future strategies of cartilage or bone TE

DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis

Little is known about frequency, association with clinical characteristics, and prognostic impact of DNA copy number alterations (CNA) on survival in central primitive neuroectodermal tumors (CNS-PNET) and tumors of the pineal region. Searches of MEDLINE, Pubmed, and EMBASE—after the original description of comparative genomic hybridization in 1992 and July 2010—identified 15 case series of patients with CNS-PNET and tumors of the pineal region whose tumors were investigated for genome-wide CNA. One additional case study was identified from contact with experts. Individual patient data were extracted from publications or obtained from investigators, and CNAs were converted to a digitized format suitable for data mining and subgroup identification. Summary profiles for genomic imbalances were generated from case-specific data. Overall survival (OS) was estimated using the Kaplan-Meier method, and by univariable and multivariable Cox regression models. In their overall CNA profiles, low grade tumors of the pineal region clearly diverged from CNS-PNET and pineoblastoma. At a median follow-up of 89months, 7-year OS rates of CNS-PNET, pineoblastoma, and low grade tumors of the pineal region were 22.9±6, 0±0, and 87.5±12%, respectively. Multivariable analysis revealed that histology (CNS-PNET), age (≤2.5years), and possibly recurrent CNAs were associated with unfavorable OS. DNA copy number profiling suggests a close relationship between CNS-PNET and pineoblastoma. Low grade tumors of the pineal region differed from CNS-PNET and pineoblastoma. Due to their high biological and clinical variability, a coordinated prospective validation in future studies is necessary to establish robust risk factor

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification

Modeling of GERDA Phase II data

The GERmanium Detector Array (GERDA) experiment at the Gran Sasso underground laboratory (LNGS) of INFN is searching for neutrinoless double-beta ($0\nu\beta\beta$) decay of $^{76}$Ge. The technological challenge of GERDA is to operate in a "background-free" regime in the region of interest (ROI) after analysis cuts for the full 100$\,$kg$\cdot$yr target exposure of the experiment. A careful modeling and decomposition of the full-range energy spectrum is essential to predict the shape and composition of events in the ROI around $Q_{\beta\beta}$ for the $0\nu\beta\beta$ search, to extract a precise measurement of the half-life of the double-beta decay mode with neutrinos ($2\nu\beta\beta$) and in order to identify the location of residual impurities. The latter will permit future experiments to build strategies in order to further lower the background and achieve even better sensitivities. In this article the background decomposition prior to analysis cuts is presented for GERDA Phase II. The background model fit yields a flat spectrum in the ROI with a background index (BI) of $16.04^{+0.78}_{-0.85} \cdot 10^{-3}\,$cts/(kg$\cdot$keV$\cdot$yr) for the enriched BEGe data set and $14.68^{+0.47}_{-0.52} \cdot 10^{-3}\,$cts/(kg$\cdot$keV$\cdot$yr) for the enriched coaxial data set. These values are similar to the one of Gerda Phase I despite a much larger number of detectors and hence radioactive hardware components

Modeling of GERDA Phase II data

The GERmanium Detector Array (Gerda) experiment at the Gran Sasso underground laboratory (LNGS) of INFN is searching for neutrinoless double-beta (0νββ) decay of 76Ge. The technological challenge of Gerda is to operate in a “background-free” regime in the region of interest (ROI) after analysis cuts for the full 100 kg·yr target exposure of the experiment. A careful modeling and decomposition of the full-range energy spectrum is essential to predict the shape and composition of events in the ROI around Qββ for the 0νββ search, to extract a precise measurement of the half-life of the double-beta decay mode with neutrinos (2νββ) and in order to identify the location of residual impurities. The latter will permit future experiments to build strategies in order to further lower the background and achieve even better sensitivities. In this article the background decomposition prior to analysis cuts is presented for Gerda Phase II. The background model fit yields a flat spectrum in the ROI with a background index (BI) of 16.04+0.78−0.85⋅10−3 cts/(keV·kg·yr) for the enriched BEGe data set and 14.68+0.47−0.52⋅10−3 cts/(keV·kg·yr) for the enriched coaxial data set. These values are similar to the one of Phase I despite a much larger number of detectors and hence radioactive hardware components

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Approaching new biomaterials: copolymerization characteristics of vinyl esters with norbornenes, allyl esters and allyl ethers

Vinyl ester-based monomers for radical photopolymerization have recently been shown to be promising alternatives to (meth)acrylates through lower irritancy and cytotoxicity. Vinyl ester monomers are becoming increasingly important on account of new, more cost-efficient synthetic production methods, not to forget their increased reactivity and improved material properties in combination with thiol–ene polymerization. Due to their biocompatibility and degradability, these monomers are more frequently used in tissue engineering. Nevertheless, the material properties can be improved by possible copolymerizations with other monomers. Therefore, the copolymerization behavior of vinyl ester with norbornene, allyl ether and allyl ester has been studied fundamentally in a photoreactor via free radical photopolymerization. Here, the consumption of double bonds of the monomers has been identified using NMR spectroscopy. Copolymerization parameters have been determined using the Kelen–Tüdös method. Results show equal consumption of vinyl ester and co-monomer double bonds leading to alternating copolymerizations. The double bond conversion was confirmed via in situ real-time near-infrared photorheology. Mono- and difunctional vinyl esters with co-monomers have also provided further insight into the polymer network of these copolymers.CDG Christian Doppler Forschungsgesellschaft17