Atypical Neurogenesis in Induced Pluripotent Stem Cells From Autistic Individuals

BACKGROUND: Autism is a heterogeneous collection of disorders with a complex molecular underpinning. Evidence from postmortem brain studies have indicated that early prenatal development may be altered in autism. Induced pluripotent stem cells (iPSCs) generated from individuals with autism with macrocephaly also indicate prenatal development as a critical period for this condition. But little is known about early altered cellular events during prenatal stages in autism. METHODS: iPSCs were generated from 9 unrelated individuals with autism without macrocephaly and with heterogeneous genetic backgrounds, and 6 typically developing control individuals. iPSCs were differentiated toward either cortical or midbrain fates. Gene expression and high throughput cellular phenotyping was used to characterize iPSCs at different stages of differentiation. RESULTS: A subset of autism-iPSC cortical neurons were RNA-sequenced to reveal autism-specific signatures similar to postmortem brain studies, indicating a potential common biological mechanism. Autism-iPSCs differentiated toward a cortical fate displayed impairments in the ability to self-form into neural rosettes. In addition, autism-iPSCs demonstrated significant differences in rate of cell type assignment of cortical precursors and dorsal and ventral forebrain precursors. These cellular phenotypes occurred in the absence of alterations in cell proliferation during cortical differentiation, differing from previous studies. Acquisition of cell fate during midbrain differentiation was not different between control- and autism-iPSCs. CONCLUSIONS: Taken together, our data indicate that autism-iPSCs diverge from control-iPSCs at a cellular level during early stage of neurodevelopment. This suggests that unique developmental differences associated with autism may be established at early prenatal stages

Genetic Evidence Highlights Potential Impacts of By-Catch to Cetaceans

Incidental entanglement in fishing gear is arguably the most serious threat to many populations of small cetaceans, judging by the alarming number of captured animals. However, other aspects of this threat, such as the potential capture of mother-offspring pairs or reproductive pairs, could be equally or even more significant but have rarely been evaluated. Using a combination of demographic and genetic data we provide evidence that i) Franciscana dolphin pairs that are potentially reproductive and mother-offspring pairs form temporal bonds, and ii) are entangled simultaneously. Our results highlight potential demographic and genetic impacts of by-catch to cetacean populations: the joint entanglement of mother-offspring or reproductive pairs, compared to random individuals, might exacerbate the demographic consequences of by-catch, and the loss of groups of relatives means that significant components of genetic diversity could be lost together. Given the social nature of many odontocetes (toothed cetaceans), we suggest that these potential impacts could be rather general to the group and therefore by-catch could be more detrimental than previously considered

Microbial Functional Capacity Is Preserved Within Engineered Soil Formulations Used In Mine Site Restoration

Mining of mineral resources produces substantial volumes of crushed rock based wastes that are characterised by poor physical structure and hydrology, unstable geochemistry and potentially toxic chemical conditions. Recycling of these substrates is desirable and can be achieved by blending waste with native soil to form a 'novel substrate' which may be used in future landscape restoration. However, these post-mining substrate based 'soils' are likely to contain significant abiotic constraints for both plant and microbial growth. Effective use of these novel substrates for ecosystem restoration will depend on the efficacy of stored topsoil as a potential microbial inoculum as well as the subsequent generation of key microbial soil functions originally apparent in local pristine sites. Here, using both marker gene and shotgun metagenome sequencing, we show that topsoil storage and the blending of soil and waste substrates to form planting substrates gives rise to variable bacterial and archaeal phylogenetic composition but a high degree of metabolic conservation at the community metagenome level. Our data indicates that whilst low phylogenetic conservation is apparent across substrate blends we observe high functional redundancy in relation to key soil microbial pathways, allowing the potential for functional recovery of key belowground pathways under targeted management

New prioritized value iteration for Markov decision processes

The problem of solving large Markov decision processes accurately and quickly is challenging. Since the computational effort incurred is considerable, current research focuses on finding superior acceleration techniques. For instance, the convergence properties of current solution methods depend, to a great extent, on the order of backup operations. On one hand, algorithms such as topological sorting are able to find good orderings but their overhead is usually high. On the other hand, shortest path methods, such as Dijkstra's algorithm which is based on priority queues, have been applied successfully to the solution of deterministic shortest-path Markov decision processes. Here, we propose an improved value iteration algorithm based on Dijkstra's algorithm for solving shortest path Markov decision processes. The experimental results on a stochastic shortest-path problem show the feasibility of our approach. © Springer Science+Business Media B.V. 2011.García Hernández, MDG.; Ruiz Pinales, J.; Onaindia De La Rivaherrera, E.; Aviña Cervantes, JG.; Ledesma Orozco, S.; Alvarado Mendez, E.; Reyes Ballesteros, A. (2012). New prioritized value iteration for Markov decision processes. Artificial Intelligence Review. 37(2):157-167. doi:10.1007/s10462-011-9224-zS157167372Agrawal S, Roth D (2002) Learning a sparse representation for object detection. In: Proceedings of the 7th European conference on computer vision. Copenhagen, Denmark, pp 1–15Bellman RE (1954) The theory of dynamic programming. Bull Amer Math Soc 60: 503–516Bellman RE (1957) Dynamic programming. Princeton University Press, New JerseyBertsekas DP (1995) Dynamic programming and optimal control. Athena Scientific, MassachusettsBhuma K, Goldsmith J (2003) Bidirectional LAO* algorithm. 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Cumbria, UKBoutilier C, Dean T, Hanks S (1999) Decision-theoretic planning: structural assumptions and computational leverage. J Artif Intell Res 11: 1–94Chang I, Soo H (2007) Simulation-based algorithms for Markov decision processes Communications and control engineering. Springer, LondonDai P, Goldsmith J (2007a) Faster dynamic programming for Markov decision processes. Technical report. Doctoral consortium, department of computer science and engineering. University of WashingtonDai P, Goldsmith J (2007b) Topological value iteration algorithm for Markov decision processes. In: Proceedings of the 20th international joint conference on artificial intelligence. Hyderabad, India, pp 1860–1865Dai P, Hansen EA (2007c) Prioritizing bellman backups without a priority queue. In: Proceedings of the 17th international conference on automated planning and scheduling, association for the advancement of artificial intelligence. Rhode Island, USA, pp 113–119Dibangoye JS, Chaib-draa B, Mouaddib A (2008) A Novel prioritization technique for solving Markov decision processes. In: Proceedings of the 21st international FLAIRS (The Florida Artificial Intelligence Research Society) conference, association for the advancement of artificial intelligence. Florida, USAFerguson D, Stentz A (2004) Focused propagation of MDPs for path planning. In: Proceedings of the 16th IEEE international conference on tools with artificial intelligence. pp 310–317Hansen EA, Zilberstein S (2001) LAO: a heuristic search algorithm that finds solutions with loops. Artif Intell 129: 35–62Hinderer K, Waldmann KH (2003) The critical discount factor for finite Markovian decision processes with an absorbing set. Math Methods Oper Res 57: 1–19Li L (2009) A unifying framework for computational reinforcement learning theory. PhD Thesis. The state university of New Jersey, New Brunswick. NJLittman ML, Dean TL, Kaelbling LP (1995) On the complexity of solving Markov decision problems.In: Proceedings of the 11th international conference on uncertainty in artificial intelligence. Montreal, Quebec pp 394–402McMahan HB, Gordon G (2005a) Fast exact planning in Markov decision processes. In: Proceedings of the 15th international conference on automated planning and scheduling. Monterey, CA, USAMcMahan HB, Gordon G (2005b) Generalizing Dijkstra’s algorithm and gaussian elimination for solving MDPs. Technical report, Carnegie Mellon University, PittsburghMeuleau N, Brafman R, Benazera E (2006) Stochastic over-subscription planning using hierarchies of MDPs. In: Proceedings of the 16th international conference on automated planning and scheduling. Cumbria, UK, pp 121–130Moore A, Atkeson C (1993) Prioritized sweeping: reinforcement learning with less data and less real time. Mach Learn 13: 103–130Puterman ML (1994) Markov decision processes. 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Mammalian microRNAs predominantly act to decrease target mRNA levels

MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.National Institutes of Health (U.S.

Long-term biochemical results after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy for high risk prostate cancer

Abstract Background Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.</p

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure