ForewordThe study of the fundamental structure of nuclear matter is a central thrust of physics research in the United States. As indicated in Frontiers of Nuclear Science, the 2007 Nuclear Science Advisory Committee long range plan, consideration of a future Electron-Ion Collider (EIC) is a priority and will likely be a significant focus of discussion at the next long range plan. We are therefore pleased to have supported the ten week program in fall 2010 at the Institute of Nuclear Theory which examined at length the science case for the EIC. This program was a major effort; it attracted the maximum allowable attendance over ten weeks.This report summarizes the current understanding of the physics and articulates important open questions that can be addressed by an EIC. It converges towards a set of "golden" experiments that illustrate both the science reach and the technical demands on such a facility, and thereby establishes a firm ground from which to launch the next phase in preparation for the upcoming long range plan discussions. We thank all the participants in this productive program. In particular, we would like to acknowledge the leadership and dedication of the five co-organizers of the program who are also the co-editors of this report.David Kaplan, Director, National Institute for Nuclear Theory Hugh Montgomery, Director, Thomas Jefferson National Accelerator Facility Steven Vigdor, Associate Lab Director, Brookhaven National Laboratory iii Preface This volume is based on a ten-week program on "Gluons and the quark sea at high energies", which took place at the Institute for Nuclear Theory (INT) in Seattle from September 13 to November 19, 2010. The principal aim of the program was to develop and sharpen the science case for an Electron-Ion Collider (EIC), a facility that will be able to collide electrons and positrons with polarized protons and with light to heavy nuclei at high energies, offering unprecedented possibilities for in-depth studies of quantum chromodynamics. Guiding questions were• What are the crucial science issues?• How do they fit within the overall goals for nuclear physics?• Why can't they be addressed adequately at existing facilities?• Will they still be interesting in the 2020's, when a suitable facility might be realized?The program started with a five-day workshop on "Perturbative and Non-Perturbative Aspects of QCD at Collider Energies", which was followed by eight weeks of regular program and a concluding four-day workshop on "The Science Case for an EIC".More than 120 theorists and experimentalists took part in the program over ten weeks. It was only possible to smoothly accommodate such a large number of participants because of the extraordinary efforts of the INT staff, to whom we extend our warm thanks and appreciation. We thank the INT Director, David Kaplan, for his strong support of the program and for covering a significant portion of the costs for printing this volume. We gratefully acknowledge additional financial support provided by BNL and JLab.The program w...

Many organisms have a mechanism for down regulating the expression of non-synapsed chromosomes and chromosomal regions during meiosis. This phenomenon is thought to function in genome defense. During early meiosis in Caenorhabditis elegans, unpaired chromosomes (e.g., the male X chromosome) become enriched for a modification associated with heterochromatin and transcriptional repression, dimethylation of histone H3 on lysine 9 (H3K9me2). This enrichment requires activity of the cellular RNA-directed RNA polymerase, EGO-1. Here we use genetic mutation, RNA interference, immunofluorescence microscopy, fluorescence in situ hybridization, and molecular cloning methods to identify and analyze three additional regulators of meiotic H3K9me2 distribution: CSR-1 (a Piwi/PAZ/Argonaute protein), EKL-1 (a Tudor domain protein), and DRH-3 (a DEAH/D-box helicase). In csr-1, ekl-1, and drh-3 mutant males, we observed a reduction in H3K9me2 accumulation on the unpaired X chromosome and an increase in H3K9me2 accumulation on paired autosomes relative to controls. We observed a similar shift in H3K9me2 pattern in hermaphrodites that carry unpaired chromosomes. Based on several assays, we conclude that ectopic H3K9me2 accumulates on paired and synapsed chromosomes in these mutants. We propose alternative models for how a small RNA-mediated pathway may regulate H3K9me2 accumulation during meiosis. We also describe the germline phenotypes of csr-1, ekl-1, and drh-3 mutants. Our genetic data suggest that these factors, together with EGO-1, participate in a regulatory network to promote diverse aspects of development.

Biocompatible calcium phosphate ceramic grafts are able of supporting new bone formation in appropriate environment. The major limitation of these materials usage for medical implants is the absence of accessible methods for their patient-specific fabrication. 3D printing methodology is an excellent approach to overcome the limitation supporting effective and fast fabrication of individual complex bone substitutes. Here, we proposed a relatively simple route for 3D printing of octacalcium phosphates (OCP) in complexly shaped structures by the combination of inkjet printing with post-treatment methodology. The printed OCP blocks were further implanted in the developed cranial bone defect followed by histological evaluation. The obtained result confirmed the potential of the developed OCP bone substitutes, which allowed 2.5-time reducing of defect’s diameter at 6.5 months in a region where native bone repair is extremely inefficient.

Bioceramics are used to treat bone defects but in general do not induce formation of new bone, which is essential for regeneration process. Many aspects related to bioceramics synthesis, properties and biological response that are still unknown and, there is a great need for further development. In the most recent research efforts were aimed on creation of materials from biological precursors of apatite formation in humans. One possible precursor is octacalcium phosphate (OCP), which is believed to not only exhibit osteoconductivity but possess osteoinductive quality, the ability to induce bone formation. Here we propose a relatively simple route for OCP ceramics preparation with a specifically designed microstructure. Comprehensive study for OCP ceramics including biodegradation, osteogenic properties in ortopic and heterotopic models and limited clinical trials were performed that demonstrated enhanced biological behavior. Our results provide a possible new concept for the clinical applications of OCP ceramics.

In search for a new pro-angiogenic scaffold material suitable for skin bioengineering and grafting therapy, we have fabricated a number of composite sodium alginate (AG)-fibrinogen (FG) sponge scaffolds using the freeze-drying approach. Thrombin was added to drive FG/fibrin conversion, while ε-aminocapronic acid (εAc) was used as antifibrinolytic component. The slow rates of scaffold biodegradation were achieved by using Ca and Mg cations as cross-linking agents. The novel thrombin-modified AG-FG scaffolds with highly interconnected porous structure were evaluated using scanning electron microscopy, tensile testing and pycnometric analysis. The scaffolds were characterized by high porosity and tensile strength, possessing average pore size from about 60 to 300 μm depending on AG/FG ratio and fibrin stabilization. The biocompatibility of thrombin-modified scaffolds with a different AG/FG ratio was tested on human cells with potential applicability to skin tissue engineering: immortalized epidermal keratinocytes (N-TERT), primary skin fibroblasts, endothelial cells (HUVEC) and subcutaneous adipose-derived stromal cells. The scaffolds with low (15%) FG content have shown the highest adhesiveness and survival rates for all types of cells, as compared to the scaffolds with higher FG content. In unstabilized scaffolds, the addition of FG did not stimulate the aortic ring sprouting. At the same time, fibrin stabilization by εAc resulted in significant increase of aortic ring sprouting and more efficient formation of microvascular network. Altogether, obtained results suggest that thrombin-modified alginate sponges can be successfully used as a grafting material by itself to promote skin healing and regeneration and also as a scaffold for three-dimensional bioequivalent construction.

Biocompatible ceramic fillers are capable of sustaining bone formation in the proper environment. The major drawback of these scaffolding materials is the absence of osteoinductivity. To overcome this limitation, bioengineered scaffolds combine osteoconductive components (biomaterials) with osteogenic features such as cells and growth factors. The bone marrow mesenchymal stromal cells (BMMSCs) and the β-tricalcium phosphate (β-TCP) are well-known and characterized in this regard. The present study was conducted to compare the properties of novel octacalcium phosphate ceramic (OCP) granules with β-TCP (Cerasorb(®)), gingiva-derived mesenchymal stromal cells (GMSCs) properties with the BMMSCs and osteogenic and angiogenic properties of a bioengineered composite based on OCP granules and the GMSCs. This study demonstrates that GMSCs and BMMSСs have a similar osteogenic capacity. The usage of OCP ceramic granules in combination with BMMSCs/GMSCs significantly affects the osteo- and angiogenesis in bone grafts of ectopic models.

The nature of precursor phase during the biomineralization process of bone tissue formation is still controversial. Several phases were hypothesized, among them octacalcium phosphate. In this study, an in situ monitoring of structural changes, taking place upon the octacalcium phosphate bone cement hardening, was carried out in the presence of biopolymer chitosan and simulated body fluid (SBF). Several systems with different combinations of components were studied. The energy dispersive X-ray diffraction was applied to study the structural changes in real time, while morphological properties of the systems were investigated by the scanning electron microscopy. The obtained results evidence that final hydroxyapatite phase is formed only in the presence of chitosan and/or SBF, providing new insights into the in vivo biomineralization mechanism and, consequently, favoring the development of new approaches in biomaterials technology.

The calcium phosphate particles can be used as building blocks for fabrication of 3D scaffolds intended for bone tissue engineering. This work presents for the first time a rapid creation of 3D scaffolds using magnetic levitation of calcium phosphate particles. Namely, tricalcium phosphate particles of equal size and certain porosity are used, which undergo the process of recrystallization after magnetic levitational assembly of the scaffold to ensure stitching of the scaffold. Label-free levitational assembly is achieved by using a custom-designed magnetic system in the presence of gadolinium salts, which allows the levitation of calcium phosphate particles. Chemical transformation of tricalcium-to octacalcium phosphate under the condition of magnetic levitation in non-homogeneous magnetic field is also demonstrated. This approach allows obtaining rapidly the octacalcium phosphate phase in the final 3D product, which is biocompatible.