Multifragmentation and the liquid-gas phase transition: an experimental overview

Two roads are presently being followed in order to establish the existence of a liquid-gas phase transition in finite nuclear systems from nuclear reactions at high energy. The clean experiment of observing the thermodynamic properties of a finite number of nucleons in a container is presently only possible with the computer. Performed with advanced nuclear transport models, it has revealed the first-order character of the transition and allowed the extraction of the pertinent thermodynamic parameters. The validity of the applied theory is being confirmed by comparing its predictions for heavy-ion reactions with exclusive experiments. The second approach is experimentally more direct. Signals of the transition are searched for by analysing reaction data within the framework of thermodynamics of small systems. A variety of potential signals has been investigated and found to be qualitatively consistent with the expectations for the phase transition. Many of them are well reproduced with percolation models which places the nuclear fragmentation into the more general context of partitioning phenomena in finite systems. A wealth of new data on this subject has been obtained in recent experiments, some of them with a new generation of multi-detector devices aiming at higher resolutions, isotopic identification of the fragments, and the coincident detection of neutrons. Isotopic effects in multifragmentation were addressed quite intensively, with particular attention being given to their relation to the symmetry energy and its dependence on density.Comment: 10 pages, 7 figures, Contribution to Proceedings of INPC2004, Goeteborg, Sweden, June 27 - July 2, 200

Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocyte cells through the classical EPO receptor

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in non-hematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP)). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects

Interaction and filling induced quantum phases of dual Mott insulators of bosons and fermions

Many-body effects are at the very heart of diverse phenomena found in condensed-matter physics. One striking example is the Mott insulator phase where conductivity is suppressed as a result of a strong repulsive interaction. Advances in cold atom physics have led to the realization of the Mott insulating phases of atoms in an optical lattice, mimicking the corresponding condensed matter systems. Here, we explore an exotic strongly-correlated system of Interacting Dual Mott Insulators of bosons and fermions. We reveal that an inter-species interaction between bosons and fermions drastically modifies each Mott insulator, causing effects that include melting, generation of composite particles, an anti-correlated phase, and complete phase-separation. Comparisons between the experimental results and numerical simulations indicate intrinsic adiabatic heating and cooling for the attractively and repulsively interacting dual Mott Insulators, respectively

Caloric curves and critical behavior in nuclei

Data from a number of different experimental measurements have been used to construct caloric curves for five different regions of nuclear mass. These curves are qualitatively similar and exhibit plateaus at the higher excitation energies. The limiting temperatures represented by the plateaus decrease with increasing nuclear mass and are in very good agreement with results of recent calculations employing either a chiral symmetry model or the Gogny interaction. This agreement strongly favors a soft equation of state. Evidence is presented that critical excitation energies and critical temperatures for nuclei can be determined over a large mass range when the mass variations inherent in many caloric curve measurements are taken into account.Comment: In response to referees comments we have improved the discussion of the figures and added a new figure showing the relationship between the effective level density and the excitation energy. The discussion has been reordered and comments are made on recent data which support the hypothesis of a mass dependence of caloric curve

Quantum Computing and Quantum Simulation with Group-II Atoms

Recent experimental progress in controlling neutral group-II atoms for optical clocks, and in the production of degenerate gases with group-II atoms has given rise to novel opportunities to address challenges in quantum computing and quantum simulation. In these systems, it is possible to encode qubits in nuclear spin states, which are decoupled from the electronic state in the $^1$S$_0$ ground state and the long-lived $^3$P$_0$ metastable state on the clock transition. This leads to quantum computing scenarios where qubits are stored in long lived nuclear spin states, while electronic states can be accessed independently, for cooling of the atoms, as well as manipulation and readout of the qubits. The high nuclear spin in some fermionic isotopes also offers opportunities for the encoding of multiple qubits on a single atom, as well as providing an opportunity for studying many-body physics in systems with a high spin symmetry. Here we review recent experimental and theoretical progress in these areas, and summarise the advantages and challenges for quantum computing and quantum simulation with group-II atoms.Comment: 11 pages, 7 figures, review for special issue of "Quantum Information Processing" on "Quantum Information with Neutral Particles

The dynamic stator stalk of rotary ATPases

Rotary ATPases couple ATP hydrolysis/synthesis with proton translocation across biological membranes and so are central components of the biological energy conversion machinery. Their peripheral stalks are essential components that counteract torque generated by rotation of the central stalk during ATP synthesis or hydrolysis. Here we present a 2.25-Å resolution crystal structure of the peripheral stalk from Thermus thermophilus A-type ATPase/synthase. We identify bending and twisting motions inherent within the structure that accommodate and complement a radial wobbling of the ATPase headgroup as it progresses through its catalytic cycles, while still retaining azimuthal stiffness necessary to counteract rotation of the central stalk. The conformational freedom of the peripheral stalk is dictated by its unusual right-handed coiled-coil architecture, which is in principle conserved across all rotary ATPases. In context of the intact enzyme, the dynamics of the peripheral stalks provides a potential mechanism for cooperativity between distant parts of rotary ATPases

Principles of early human development and germ cell program from conserved model systems

Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during week 2-3 of early postimplantation development(1). Using in vitro models of hPGC induction(2-4), recent studies suggest striking mechanistic differences in specification of human and mouse PGCs(5). This may partly be due to the divergence in their pluripotency networks, and early postimplantation development(6-8). Since early human embryos are inaccessible for direct studies, we considered alternatives, including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs (pPGCs) originate from the posterior pre-primitive streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. Together with human and monkey in vitro models simulating peri-gastrulation development, we show conserved principles for epiblast development for competency for PGC fate, followed by initiation of the epigenetic program(9-11), regulated by a balanced SOX17–BLIMP1 gene dosage. Our combinatorial approach using human, porcine and monkey in vivo and in vitro models, provides synthetic insights on early human development

Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR

We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR −/−) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37°C for up to 9 days and displayed a terminal half-life (T1/2β) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that 125I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of' 111In-labelled ch806 was demonstrated with uptake of 31%ID g−1 and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent

Immunohistochemical discrimination of wild-type EGFR from EGFRvIII in fixed tumour specimens using anti-EGFR mAbs ICR9 and ICR10

Background:The human epidermal growth factor receptor (EGFR) is an important therapeutic target in oncology, and three different types of EGFR inhibitors have been approved for the treatment of cancer patients. However, there has been no clear association between the expression levels of EGFR protein in the tumours determined by the FDA-approved EGFR PharmDx kit (Dako) or other standard anti-EGFR antibodies and the response to the EGFR inhibitors.Method:In this study, we investigated the potential of our anti-EGFR monoclonal antibodies (mAbs; ICR9, ICR10, ICR16) for immunohistochemical diagnosis of wild-type EGFR and/or the type-III deletion mutant form of EGFR (EGFRvIII) in formalin-fixed, paraffin-embedded human tumour specimens.Results:We found that the anti-EGFR mAb in the EGFR PharmDx kit stained both wild-type and EGFRvIII-expressing cells in formalin-fixed, paraffin-embedded sections. This pattern of EGFR immunostaining was also found with our anti-EGFR mAb ICR16. In contrast, mAbs ICR10 and ICR9 were specific for the wild-type EGFR.Conclusion:We conclude that mAbs ICR9 and ICR10 are ideal tools for investigating the expression patterns of wild-type EGFR protein in tumour specimens using immunohistochemistry, and to determine their prognostic significance, as well as predictive value for response to therapy with EGFR antibodies.British Journal of Cancer advance online publication, 7 February 2012; doi:10.1038/bjc.2012.27 www.bjcancer.com

Erythropoietin: a multimodal neuroprotective agent

The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent