The Assembly of Diversity in the Morphologies and Stellar Populations of High-Redshift Galaxies

We have studied the evolution in the morphologies, sizes, stellar-masses, colors, and internal color dispersion (ICD) of galaxies at z=1 and 2.3, using a near-IR, flux-limited catalog for the HDF-N. At z=1 most luminous galaxies have morphologies of early-to-mid Hubble-types, and many show transformations between their rest-frame UV-optical morphologies. Galaxies at z=2.3 have compact and irregular morphologies with no clearly evident Hubble-sequence candidates. The mean galaxy size grows from z=2.3 to 1 by 40%, and the density of galaxies larger than 3 kpc increases by 7 times. At z=1, the size-luminosity distribution is broadly consistent with that of local galaxies, with passive evolution. However, galaxies at z=2.3 are smaller than the large present-day galaxies, and must continue to grow in size and stellar mass. We have measured the galaxies' UV-optical ICD, which quantifies differences in morphology and the relative amount of on-going star-formation. The mean and scatter in galaxies' total colors and ICD increase from z=2.3 to 1. At z=1 many galaxies with large ICD are spirals, with a few irregular systems. Few z=2.3 galaxies have high ICD, and those that do are actively merging. We interpret this as evidence for the presence of older and more diverse stellar populations at z=1 that are not generally present at z>2. We conclude that the star-formation histories of galaxies at z>2 are dominated by discrete, recurrent bursts, which quickly homogenize the galaxies' stellar content, and are possibly associated with mergers. The increase in the stellar-population diversification by z<1.4 implies that merger-induced starbursts occur less frequently than at higher redshifts, and more quiescent star-forming modes dominate. This transition coincides with the emergence of Hubble-sequence galaxies. [Abridged]Comment: Accepted for publication in the Astrophysical Journal. 20 pages, in emulateapj forma

NPTX1 Regulates Neural Lineage Specification from Human Pluripotent Stem Cells

SummaryNeural induction is the first fundamental step in nervous system formation. During development, a tightly regulated niche modulates transient extracellular signals to influence neural lineage commitment. To date, however, the cascade of molecular events that sustain these signals in humans is not well understood. Here we show that NPTX1, a secreted protein, is rapidly upregulated during neural induction from human pluripotent stem cells (hPSCs). By manipulating its expression, we were able to reduce or initiate neural lineage commitment. A time-course transcriptome analysis and functional assays show that NPTX1 acts in part by binding the Nodal receptor cofactor TDGF1, reducing both Nodal and BMP signaling. Our findings identify one of the earliest genes expressed upon neural induction and provide insight into human neural lineage specification

Twisting of X-ray isophotes in triaxial galaxies

We investigate X-ray isophote twists created by triaxiality differences between the luminous stellar distributions and the dark halos in elliptical galaxies. For a typically oblate luminous galaxy embedded in a more prolate halo formed by dissipationless collapse, the triaxiality difference of \Delta T = ~0.7 leads to typical isophote twists of = ~16 deg +/- 19 deg at 3 stellar effective radii. In a model which includes baryonic dissipation the effect is smaller, with \Delta T = ~0.3 and = ~5 deg +/- 8 deg. Thus, accurate measurements of X-ray isophote twists may be able to set constraints on the interactions between baryons and dissipationless dark matter during galaxy formation. The 30-deg X-ray isophote twist in the E4 galaxy NGC 720 cannot be reproduced by our model, suggesting an intrinsic misalignment between the halo and the stars rather than a projection effect.Comment: 18 pages, with 9 inline Postscript figures, LaTeX, aaspp4.sty, submitted to ApJ; postscript paper w/figs (200 kb) also avaliable at http://cfa-www.harvard.edu/~romanow/int.email.v2.ps.g

Globally convergent hybridization of particle swarm optimization using line search-based derivative-free techniques

The hybrid use of exact and heuristic derivative-free methods for global unconstrained optimization problems is presented. Many real-world problems are modeled by computationally expensive functions, such as problems in simulationbased design of complex engineering systems. Objective-function values are often provided by systems of partial differential equations, solved by computationally expensive black-box tools. The objective-function is likely noisy and its derivatives are not provided. On the one hand, the use of exact optimization methods might be computationally too expensive, especially if asymptotic convergence properties are sought. On the other hand, heuristic methods do not guarantee the stationarity of their final solutions. Nevertheless, heuristic methods are usually able to provide an approximate solution at a reasonable computational cost, and have been widely applied to real-world simulation-based design optimization problems. Herein, an overall hybrid algorithm combining the appealing properties of both exact and heuristic methods is discussed, with focus on Particle Swarm Optimization (PSO) and line search-based derivative-free algorithms. The theoretical properties of the hybrid algorithm are detailed, in terms of limit points stationarity. Numerical results are presented for a test function and for two real-world optimization problems in ship hydrodynamics.The hybrid use of exact and heuristic derivative-free methods for global unconstrained optimization problems is presented. Many real-world problems are modeled by computationally expensive functions, such as problems in simulationbased design of complex engineering systems. Objective-function values are often provided by systems of partial differential equations, solved by computationally expensive black-box tools. The objective-function is likely noisy and its derivatives are often not available. On the one hand, the use of exact optimization methods might be computationally too expensive, especially if asymptotic convergence properties are sought. On the other hand, heuristic methods do not guarantee the stationarity of their final solutions. Nevertheless, heuristic methods are usually able to provide an approximate solution at a reasonable computational cost, and have been widely applied to real-world simulation-based design optimization problems. Herein, an overall hybrid algorithm combining the appealing properties of both exact and heuristic methods is discussed, with focus on Particle Swarm Optimization (PSO) and line search-based derivative-free algorithms. The theoretical properties of the hybrid algorithm are detailed, in terms of limit points stationarity. Numerical results are presented for a specific test function and for two real-world optimization problems in ship hydrodynamics

H alpha Star Formation Rates in Massive Galaxies at z ~ 1

We present a near-infrared spectroscopic study of a stellar mass selected sample of galaxies at z~1 utilising the LIRIS multi-object spectrograph on the WHT. We detect continuum, and the H alpha line for our sample, which is one of the better direct tracers of star formation in external galaxies. We spectroscopically measure the H alpha emission from 41 massive (M_{*}>10^{10.5} Msol) galaxies taken from the POWIR Survey with spectroscopic redshifts 0.4<z_{spec}<1.4. We correct our H alpha fluxes for dust extinction by using multi-wavelength data, and investigate SFR trends with mass and colour. We find a drop in the fraction of massive galaxies with M_{*}>10^{11} Msol which are detected in H alpha emission at z<0.9. We furthermore find that the fraction of galaxies with H alpha emission drops steadily and significantly with redder (U-B) colours at z~1, and that the SSFR drops with increasing (U-B) colour for galaxies at all masses. By investigating the SFR-mass relation we find that the SFR is roughly constant with mass, in possible contrast to previous work, and that the specific star formation rate (SSFR) is lower in the most massive galaxies. The scatter in the SFR vs. mass relationship is very small for those systems with ongoing star formation which suggests that star formation in the most massive galaxies at z~1 shuts off rather abruptly over <1 Gyr, without an obvious gradual decline. We furthermore investigate the SFR as a function of (U-B) colour divided into different mass bins, revealing a tracer of the epoch of transition from star forming to passive, as a form of star formation "downsizing". This suggests that the shut off of star formation occurs before the change in a galaxy's colour. We find that galaxy stellar mass is the primary driving mechanisms behind the star formation history for these galaxies and discuss several possible mechanisms for regulating this process.Comment: 20 pages, accepted for publication in MNRA

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Directed differentiation of embryonic stem cells using a bead-based combinatorial screening method

We have developed a rapid, bead-based combinatorial screening method to determine optimal combinations of variables that direct stem cell differentiation to produce known or novel cell types having pre-determined characteristics. Here we describe three experiments comprising stepwise exposure of mouse or human embryonic cells to 10,000 combinations of serum-free differentiation media, through which we discovered multiple novel, efficient and robust protocols to generate a number of specific hematopoietic and neural lineages. We further demonstrate that the technology can be used to optimize existing protocols in order to substitute costly growth factors with bioactive small molecules and/or increase cell yield, and to identify in vitro conditions for the production of rare developmental intermediates such as an embryonic lymphoid progenitor cell that has not previously been reported

Supramolecular template-directed synthesis of triazole oligomers.

Sandwich complexes formed by two zinc porphyrins and a diamine ligand (DABCO) have been used as a supramolecular template to direct the synthesis of triazole oligomers. Monomer units equipped with two polymerizable functional groups, an alkyne and an azide, were attached to the template via ester bonds between a phenol unit on the monomer and benzoic acid units on the porphyrin. Self-assembly of the zinc porphyrins by addition of DABCO led to a supramolecular complex containing four of the monomer units, two on each porphyrin. CuAAC oligomerisation was carried out in the presence of a chain capping agent to prevent intermolecular reactions between the templated products, which carry reactive chain ends. The templated-directed oligomerisation resulted in selective formation of a duplex, which contains two identical chains of triazole oligomers connecting the porphyrin linkers. The effective molarity for the intramolecular CuAAC reactions on the template is 3-9 mM, and because the triazole backbone has a direction, the product duplex was obtained as a 4 : 1 mixture of the parallel and antiparallel isomers. Hydrolysis of the ester bonds connecting the oligomers to the template gave a single product, the phenol 2-mer, in excellent yield. The introduction of a supramolecular element into the template considerably broadens the scope of the covalent template-directed oligomerisation methodology that we previously developed for the replication of sequence information in synthetic oligomers.European Research Council for grants ERC-2012- AdG 320539-duplex and ERC-2020-AdG 101018984-InfoMols, and the Herchel Smith Fun