Broadband, unpolarized repumping and clearout light sources for Sr+^+ single-ion clocks

Future transportable optical clocks require compact and reliable light sources. Here, broadband, unpolarized repumper and state clearout sources for Sr+ single-ion optical clocks are reported. These turn-key devices require no frequency stabilization nor external modulators. They are fiber based, inexpensive, and compact. Key characteristics for clock operation are presented, including optical spectra, induced light shifts and required extinction ratios. Tests with an operating single-ion standard show a clearout efficiency of 100%. Compared to a laser-based repumper, the achievable fluorescence rates for ion detection are a few tens of per cent lower. The resulting ion kinetic temperature is 1--1.5 mK, near the Doppler limit of the ion system. Similar repumper light sources could be made for Ca+ (866 nm) and Ba+ (650 nm) using semiconductor gain media.Comment: 4 pages, 6 figure

Strong Spherical Asymptotics for Rotor-Router Aggregation and the Divisible Sandpile

The rotor-router model is a deterministic analogue of random walk. It can be used to define a deterministic growth model analogous to internal DLA. We prove that the asymptotic shape of this model is a Euclidean ball, in a sense which is stronger than our earlier work. For the shape consisting of $n=\omega_d r^d$ sites, where $\omega_d$ is the volume of the unit ball in $\R^d$, we show that the inradius of the set of occupied sites is at least $r-O(\log r)$, while the outradius is at most $r+O(r^\alpha)$ for any $\alpha > 1-1/d$. For a related model, the divisible sandpile, we show that the domain of occupied sites is a Euclidean ball with error in the radius a constant independent of the total mass. For the classical abelian sandpile model in two dimensions, with $n=\pi r^2$ particles, we show that the inradius is at least $r/\sqrt{3}$, and the outradius is at most $(r+o(r))/\sqrt{2}$. This improves on bounds of Le Borgne and Rossin. Similar bounds apply in higher dimensions.Comment: [v3] Added Theorem 4.1, which generalizes Theorem 1.4 for the abelian sandpile. [v4] Added references and improved exposition in sections 2 and 4. [v5] Final version, to appear in Potential Analysi

Scaling limits of coupled continuous time random walks and residual order statistics through marked point processes

A continuous time random walk (CTRW) is a random walk in which both spatial changes represented by jumps and waiting times between the jumps are random. The CTRW is coupled if a jump and its preceding or following waiting time are dependent random variables, respectively. The aim of this paper is to explain the occurrence of different limit processes for CTRWs with forward- or backward-coupling in Straka and Henry (2011) using marked point processes. We also establish a series representation for the different limits. The methods used also allow us to solve an open problem concerning residual order statistics by LePage (1981).Comment: revised version, to appear in: Stoch. Process. App

Mutation, selection, and ancestry in branching models: a variational approach

We consider the evolution of populations under the joint action of mutation and differential reproduction, or selection. The population is modelled as a finite-type Markov branching process in continuous time, and the associated genealogical tree is viewed both in the forward and the backward direction of time. The stationary type distribution of the reversed process, the so-called ancestral distribution, turns out as a key for the study of mutation-selection balance. This balance can be expressed in the form of a variational principle that quantifies the respective roles of reproduction and mutation for any possible type distribution. It shows that the mean growth rate of the population results from a competition for a maximal long-term growth rate, as given by the difference between the current mean reproduction rate, and an asymptotic decay rate related to the mutation process; this tradeoff is won by the ancestral distribution. Our main application is the quasispecies model of sequence evolution with mutation coupled to reproduction but independent across sites, and a fitness function that is invariant under permutation of sites. Here, the variational principle is worked out in detail and yields a simple, explicit result.Comment: 45 pages,8 figure

Common Carp Disrupt Ecosystem Structure and Function Through Middle-out Effects

Middle-out effects or a combination of top-down and bottom-up processes create many theoretical and empirical challenges in the realm of trophic ecology. We propose using specific autecology or species trait (i.e. behavioural) information to help explain and understand trophic dynamics that may involve complicated and nonunidirectional trophic interactions. The common carp (Cyprinus carpio) served as our model species for whole-lake observational and experimental studies; four trophic levels were measured to assess common carp-mediated middle-out effects across multiple lakes. We hypothesised that common carp could influence aquatic ecosystems through multiple pathways (i.e. abiotic and biotic foraging, early life feeding, nutrient). Both studies revealed most trophic levels were affected by common carp, highlighting strong middle-out effects likely caused by common carp foraging activities and abiotic influence (i.e. sediment resuspension). The loss of water transparency, submersed vegetation and a shift in zooplankton dynamics were the strongest effects. Trophic levels furthest from direct pathway effects were also affected (fish life history traits). The present study demonstrates that common carp can exert substantial effects on ecosystem structure and function. Species capable of middle-out effects can greatly modify communities through a variety of available pathways and are not confined to traditional top-down or bottom-up processes

Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research

A major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural stem cell (NSC) line derived from the human fetal ventral mesencephalon (hVM1). This line has been biochemically, genetically, immunocytochemically and electrophysiologically characterized to document its usefulness as a model system for the generation of A9 dopaminergic neurons (DAn). Long-term in vivo transplantation studies in parkinsonian rats showed that the grafts do not mature evenly. We reasoned that diverse clones in the hVM1 line might have different abilities to differentiate. In the present study, we have analyzed 9 hVM1 clones selected on the basis of their TH generation potential and, based on the number of v-myc copies, v-myc down-regulation after in vitro differentiation, in vivo cell cycle exit, TH+ neuron generation and expression of a neuronal mature marker (hNSE), we selected two clones for further in vivo PD cell replacement studies. The conclusion is that homogeneity and clonality of characterized NSCs allow transplantation of cells with controlled properties, which should help in the design of long-term in vivo experimentsThis work was supported by grants from the Spanish Ministry of Economy and Competitiveness (formerly Science and Innovation; PLE2009-0101, SAF2010-17167), Comunidad Autónoma Madrid (S2011-BMD-2336), Instituto Salud Carlos III (RETICS TerCel, RD06/0010/0009) and European Union (Excell, NMP4-SL-2008-214706). This work was also supported by an institutional grant from Foundation Ramón Areces to the Center of Molecular Biology Severo Ocho

Dyskinesias after neural transplantation in Parkinson's disease: what do we know and what is next?

Since the 1980 s, when cell transplantation into the brain as a cure for Parkinson's disease hit the headlines, several patients with Parkinson's disease have received transplantation of cells from aborted fetuses with the aim of replacing the dopamine cells destroyed by the disease. The results in human studies were unpredictable and raised controversy. Some patients showed remarkable improvement, but many of the patients who underwent transplantation experienced serious disabling adverse reactions, putting an end to human trials since the late 1990 s. These side effects consisted of patients' developing troublesome involuntary, uncontrolled movements in the absence of dopaminergic medication, so-called off-phase, graft-induced dyskinesias. Notwithstanding the several mechanisms having been proposed, the pathogenesis of this type of dyskinesias remained unclear and there was no effective treatment. It has been suggested that graft-induced dyskinesias could be related to fiber outgrowth from the graft causing increased dopamine release, that could be related to the failure of grafts to restore a precise distribution of dopaminergic synaptic contacts on host neurons or may also be induced by inflammatory and immune responses around the graft. A recent study, however, hypothesized that an important factor for the development of graft-induced dyskinesias could include the composition of the cell suspension and specifically that a high proportion of serotonergic neurons cografted in these transplants engage in nonphysiological properties such as false transmitter release. The findings from this study showed serotonergic hyperinnervation in the grafted striatum of two patients with Parkinson's disease who exhibited major motor recovery after transplantation with fetal mesencephalic tissue but later developed graft-induced dyskinesias. Moreover, the dyskinesias were significantly attenuated by administration of a serotonin agonist, which activates the inhibitory serotonin autoreceptors and attenuates transmitter release from serotonergic neurons, indicating that graft-induced dyskinesias were caused by the dense serotonergic innervation engaging in false transmitter release. Here the implications of the recent findings for the development of new human trials testing the safety and efficacy of cell transplantation in patients with Parkinson's disease are discussed