The role of apoptosis in the development of AGM hematopoietic stem cells revealed by Bcl-2 overexpression

Apoptosis is an essential process in embryonic tissue remodeling and adult tissue homeostasis. Within the adult hematopoietic system, it allows for tight regulation of hematopoietic cell subsets. Previously, it was shown that B-cell leukemia 2 (Bcl-2) overexpression in the adult increases the viability and activity of hematopoietic cells under normal and/or stressful conditions. However, a role for apoptosis in the embryonic hematopoietic system has not yet been established. Since the first hematopoietic stem cells (HSCs) are generated within the aortagonad-mesonephros (AGM; an actively remodeling tissue) region beginning at embryonic day 10.5, we examined this tissue for expression of apoptosis-related genes and ongoing apoptosis. Here, we show expression of several proapoptotic and antiapoptotic genes in the AGM. We also generated transgenic mice overexpressing Bcl-2 under the control of the transcriptional regulatory elements of the HSC marker stem cell antigen-1 (Sca-1), to test for the role of cell survival in the regulation of AGM HSCs. We provide evidence for increased numbers and viability of Sca-1(+) cells in the AGM and subdissected midgestation aortas, the site where HSCs are localized. Most important, our in vivo transplantation data show that Bcl-2 overexpression increases AGM and fetal liver HSC activity, strongly suggesting that apoptosis plays a role in HSC development

Large lepton asymmetry from Q-balls

We propose a scenario which can explain large lepton asymmetry and small baryon asymmetry simultaneously. Large lepton asymmetry is generated through Affleck-Dine (AD) mechanism and almost all the produced lepton numbers are absorbed into Q-balls (L-balls). If the lifetime of the L-balls is longer than the onset of electroweak phase transition but shorter than the epoch of big bang nucleosynthesis (BBN), the large lepton asymmetry in the L-balls is protected from sphaleron effects. On the other hand, small (negative) lepton numbers are evaporated from the L-balls due to thermal effects, which are converted into the observed small baryon asymmetry by virtue of sphaleron effects. Large and positive lepton asymmetry of electron type is often requested from BBN. In our scenario, choosing an appropriate flat direction in the minimal supersymmetric standard model (MSSM), we can produce positive lepton asymmetry of electron type but totally negative lepton asymmetry.Comment: 10 pages, 3 figures, ReVTeX

Spontaneous baryogenesis in flat directions

We discuss a spontaneous baryogenesis mechanism in flat directions. After identifying the Nambu-Goldstone mode which derivatively couples to the associated $U$(1) current and rotates due to the A-term, we show that spontaneous baryogenesis can be naturally realized in the context of the flat direction. As applications, we discuss two scenarios of baryogenesis in detail. One is baryogenesis in a flat direction with a vanishing $B-L$ charge, especially, with neither baryon nor lepton charge, which was recently proposed by Chiba and the present authors. The other is a baryogenesis scenario compatible with a large lepton asymmetry.Comment: 10 pages, no figure, the version accepted to Phys. Rev. D; a few explanatory comments are adde

Probability distribution of the index in gauge theory on 2d non-commutative geometry

We investigate the effects of non-commutative geometry on the topological aspects of gauge theory using a non-perturbative formulation based on the twisted reduced model. The configuration space is decomposed into topological sectors labeled by the index nu of the overlap Dirac operator satisfying the Ginsparg-Wilson relation. We study the probability distribution of nu by Monte Carlo simulation of the U(1) gauge theory on 2d non-commutative space with periodic boundary conditions. In general the distribution is asymmetric under nu -> -nu, reflecting the parity violation due to non-commutative geometry. In the continuum and infinite-volume limits, however, the distribution turns out to be dominated by the topologically trivial sector. This conclusion is consistent with the instanton calculus in the continuum theory. However, it is in striking contrast to the known results in the commutative case obtained from lattice simulation, where the distribution is Gaussian in a finite volume, but the width diverges in the infinite-volume limit. We also calculate the average action in each topological sector, and provide deeper understanding of the observed phenomenon.Comment: 16 pages,10 figures, version appeared in JHE

The index of the overlap Dirac operator on a discretized 2d non-commutative torus

The index, which is given in terms of the number of zero modes of the Dirac operator with definite chirality, plays a central role in various topological aspects of gauge theories. We investigate its properties in non-commutative geometry. As a simple example, we consider the U(1) gauge theory on a discretized 2d non-commutative torus, in which general classical solutions are known. For such backgrounds we calculate the index of the overlap Dirac operator satisfying the Ginsparg-Wilson relation. When the action is small, the topological charge defined by a naive discretization takes approximately integer values, and it agrees with the index as suggested by the index theorem. Under the same condition, the value of the index turns out to be a multiple of N, the size of the 2d lattice. By interpolating the classical solutions, we construct explicit configurations, for which the index is of order 1, but the action becomes of order N. Our results suggest that the probability of obtaining a non-zero index vanishes in the continuum limit, unlike the corresponding results in the commutative space.Comment: 22 pages, 8 figures, LaTeX, JHEP3.cls. v3:figures 1 and 2 improved (all the solutions included),version published in JHE

Prioritising research areas for antibiotic stewardship programmes in hospitals: a behavioural perspective consensus paper

SCOPE: Antibiotic stewardship programmes (ASPs) are necessary in hospitals to improve the judicious use of antibiotics. While ASPs require complex change of key behaviours on individual, team, organisation and policy levels, evidence from the behavioural sciences is underutilised in antibiotic stewardship studies across the world, including high-income countries (HICs). A consensus procedure was performed to propose research priority areas for optimising effective implementation of ASPs in hospital settings, using a behavioural perspective. METHODS: A workgroup for behavioural approaches to ASPs was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). Eighteen clinical and academic specialists in antibiotic stewardship, implementation science and behaviour change from four high-income countries with publicly-funded health care systems (that is Canada, Germany, Norway and the UK), met face-to-face to agree on broad research priority areas using a structured consensus method. QUESTION ADDRESSED AND RECOMMENDATIONS: The consensus process on the 10 identified research priority areas resulted in recommendations that need urgent scientific interest and funding to optimise effective implementation of antibiotic stewardship programmes for hospital inpatients in HICs with publicly-funded health care systems. We suggest and detail, behavioural science evidence-guided research efforts in the following areas: 1) Comprehensively identifying barriers and facilitators to implementing antibiotic stewardship programmes and clinical recommendations intended to optimise antibiotic prescribing; 2) Identifying actors ('who') and actions ('what needs to be done') of antibiotic stewardship programmes and clinical teams; 3) Synthesising available evidence to support future research and planning for antibiotic stewardship programmes; 4) Specifying the activities in current antibiotic stewardship programmes with the purpose of defining a 'control group' for comparison with new initiatives; 5) Defining a balanced set of outcomes and measures to evaluate the effects of interventions focused on reducing unnecessary exposure to antibiotics; 6) Conducting robust evaluations of antibiotic stewardship programmes with built-in process evaluations and fidelity assessments; 7) Defining and designing antibiotic stewardship programmes; 8) Establishing the evidence base for impact of antibiotic stewardship programmes on resistance; 9) Investigating the role and impact of government and policy contexts on antibiotic stewardship programmes; and 10) Understanding what matters to patients in antibiotic stewardship programmes in hospitals. Assessment, revisions and updates of our priority-setting exercise should be considered, at intervals of 2 years. To propose research priority areas in low- and medium income countries (LIMCs), the methodology reported here could be applied

Heavy Quarks and Heavy Quarkonia as Tests of Thermalization

We present here a brief summary of new results on heavy quarks and heavy quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma Thermalization" Workshop in Vienna, Austria in August 2005, directly following the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop (Vienna August 2005) Proceeding

Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The invariant differential cross section for inclusive electron production in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4 <= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Nuclear Modification of Electron Spectra and Implications for Heavy Quark Energy Loss in Au+Au Collisions at sqrt(s_NN)=200 GeV

The PHENIX experiment has measured mid-rapidity transverse momentum spectra (0.4 < p_T < 5.0 GeV/c) of electrons as a function of centrality in Au+Au collisions at sqrt(s_NN)=200 GeV. Contributions from photon conversions and from light hadron decays, mainly Dalitz decays of pi^0 and eta mesons, were removed. The resulting non-photonic electron spectra are primarily due to the semi-leptonic decays of hadrons carrying heavy quarks. Nuclear modification factors were determined by comparison to non-photonic electrons in p+p collisions. A significant suppression of electrons at high p_T is observed in central Au+Au collisions, indicating substantial energy loss of heavy quarks.Comment: 330 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV

We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and semi-central collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm