Restoration of auditory evoked responses by human ES-cell-derived otic progenitors

Deafness is a condition with a high prevalence worldwide, produced primarily by the loss of the sensory hair cells and their associated spiral ganglion neurons (SGNs). Of all the forms of deafness, auditory neuropathy is of particular concern. This condition, defined primarily by damage to the SGNs with relative preservation of the hair cells1, is responsible for a substantial proportion of patients with hearing impairment2. Although the loss of hair cells can be circumvented partially by a cochlear implant, no routine treatment is available for sensory neuron loss, as poor innervation limits the prospective performance of an implant3. Using stem cells to recover the damaged sensory circuitry is a potential therapeutic strategy. Here we present a protocol to induce differentiation from human embryonic stem cells (hESCs) using signals involved in the initial specification of the otic placode. We obtained two types of otic progenitors able to differentiate in vitro into hair-cell-like cells and auditory neurons that display expected electrophysiological properties. Moreover, when transplanted into an auditory neuropathy model, otic neuroprogenitors engraft, differentiate and significantly improve auditory-evoked response thresholds. These results should stimulate further research into the development of a cell-based therapy for deafness

SO(3) Monopoles, Level-One Seiberg-Witten Moduli Spaces, and Witten's Conjecture in Low Degrees

We prove Witten's formula relating the Donaldson and Seiberg-Witten series modulo powers of degree $c+2$, with $c=-{1/4}(7\chi+11\sigma)$, for four-manifolds obeying some mild conditions, where $\chi$ and $\sigma$ are their Euler characteristic and signature. We use the moduli space of SO(3) monopoles as a cobordism between a link of the Donaldson moduli space of anti-self-dual SO(3) connections and links of the moduli spaces of Seiberg-Witten monopoles. Gluing techniques allow us to compute contributions from Seiberg-Witten moduli spaces lying in the first (or `one-bubble') level of the Uhlenbeck compactification of the moduli space of SO(3) monopoles.Comment: Minor corrections; details added. Topology and its Applications, 91 pages, to appea

Emerging Pharmacotherapies for Adult Patients with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) treatment regimes are amongst the longest, most intensive and complex used in hematooncology. Despite this, while treatment of pediatric ALL is a success story, we are far from being able to ensure a durable response in adult ALL. This is not due to failure of induction therapy as a complete remission (CR) is achieved in over 90% of patients. However the challenge remains in ensuring a sustained remission. Furthermore in the face of relapsed disease, salvage therapies currently offer a poor chance of a good outcome. This article reviews the novel agents which show the most promise in the treatment of adult ALL

Snacking characteristics and patterns and their associations with diet quality and BMI in the Childhood Obesity Prevention and Treatment Research Consortium

Objective: To describe snacking characteristics and patterns in children and examine associations with diet quality and BMI. Design: Children's weight and height were measured. Participants/adult proxies completed multiple 24 h dietary recalls. Snack occasions were self-identified. Snack patterns were derived for each sample using exploratory factor analysis. Associations of snacking characteristics and patterns with Healthy Eating Index-2010 (HEI-2010) score and BMI were examined using multivariable linear regression models. Setting: Childhood Obesity Prevention and Treatment Research (COPTR) Consortium, USA: NET-Works, GROW, GOALS and IMPACT studies. Participants: Predominantly low-income, racial/ethnic minorities: NET-Works (n 534, 2-4-year-olds); GROW (n 610, 3-5-year-olds); GOALS (n 241, 7-11-year-olds); IMPACT (n 360, 10-13-year-olds).Results: Two snack patterns were derived for three studies: a meal-like pattern and a beverage pattern. The IMPACT study had a similar meal-like pattern and a dairy/grains pattern. A positive association was observed between meal-like pattern adherence and HEI-2010 score (P for trend < 0-01) and snack occasion frequency and HEI-2010 score (β coefficient (95 % CI): NET-Works, 0-14 (0-04, 0-23); GROW, 0-12 (0-02, 0-21)) among younger children. A preference for snacking while using a screen was inversely associated with HEI-2010 score in all studies except IMPACT (β coefficient (95 % CI): NET-Works, -3-15 (-5-37, -0-92); GROW, -2-44 (-4-27, -0-61); GOALS, -5-80 (-8-74, -2-86)). Associations with BMI were almost all null. Conclusions: Meal-like and beverage patterns described most children's snack intake, although patterns for non-Hispanic Blacks or adolescents may differ. Diets of 2-5-year-olds may benefit from frequent meal-like pattern snack consumption and diets of all children may benefit from decreasing screen use during eating occasions

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

Measurement of the Lifetime of the Tau Lepton

The tau lepton lifetime is measured with the L3 detector at LEP using the complete data taken at centre-of-mass energies around the Z pole resulting in tau_tau = 293.2 +/- 2.0 (stat) +/- 1.5 (syst) fs. The comparison of this result with the muon lifetime supports lepton universality of the weak charged current at the level of six per mille. Assuming lepton universality, the value of the strong coupling constant, alpha_s is found to be alpha_s(m_tau^2) = 0.319 +/- 0.015(exp.) +/- 0.014 (theory)

Measurement of the Tau Branching Fractions into Leptons

Using data collected with the L3 detector near the Z resonance, corresponding to an integrated luminosity of 150pb-1, the branching fractions of the tau lepton into electron and muon are measured to be B(tau->e nu nu) = (17.806 +- 0.104 (stat.) +- 0.076 (syst.)) %, B(tau->mu nu nu) = (17.342 +- 0.110 (stat.) +- 0.067 (syst.)) %. From these results the ratio of the charged current coupling constants of the muon and the electron is determined to be g_mu/g_e = 1.0007 +- 0.0051. Assuming electron-muon universality, the Fermi constant is measured in tau lepton decays as G_F = (1.1616 +- 0.0058) 10^{-5} GeV^{-2}. Furthermore, the coupling constant of the strong interaction at the tau mass scale is obtained as alpha_s(m_tau^2) = 0.322 +- 0.009 (exp.) +- 0.015 (theory)

Measurement of the Topological Branching Fractions of the tau lepton at LEP

Using data collected with the L3 detector at LEP from 1992 to 1995 on the Z peak, we determine the branching fractions of the tau lepton into one, three and five charged particles to be: B(tau->(1-prong)) = 85.274 +- 0.105 +- 0.073 %, B(tau->(3-prong)) = 14.556 +- 0.105 +- 0.076 %, B(tau->(5-prong)) = 0.170 +- 0.022 +- 0.026 %. The first uncertainties are statistical and the second systematic. The accuracy of these measurements alone is similar to that of the current world average

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix