Signaling network prediction by the Ontology Fingerprint enhanced Bayesian network

Abstract Background Despite large amounts of available genomic and proteomic data, predicting the structure and response of signaling networks is still a significant challenge. While statistical method such as Bayesian network has been explored to meet this challenge, employing existing biological knowledge for network prediction is difficult. The objective of this study is to develop a novel approach that integrates prior biological knowledge in the form of the Ontology Fingerprint to infer cell-type-specific signaling networks via data-driven Bayesian network learning; and to further use the trained model to predict cellular responses. Results We applied our novel approach to address the Predictive Signaling Network Modeling challenge of the fourth (2009) Dialog for Reverse Engineering Assessment's and Methods (DREAM4) competition. The challenge results showed that our method accurately captured signal transduction of a network of protein kinases and phosphoproteins in that the predicted protein phosphorylation levels under all experimental conditions were highly correlated (R2 = 0.93) with the observed results. Based on the evaluation of the DREAM4 organizer, our team was ranked as one of the top five best performers in predicting network structure and protein phosphorylation activity under test conditions. Conclusions Bayesian network can be used to simulate the propagation of signals in cellular systems. Incorporating the Ontology Fingerprint as prior biological knowledge allows us to efficiently infer concise signaling network structure and to accurately predict cellular responses.http://deepblue.lib.umich.edu/bitstream/2027.42/109490/1/12918_2012_Article_989.pd

RLAIF: Scaling Reinforcement Learning from Human Feedback with AI Feedback

Reinforcement learning from human feedback (RLHF) is effective at aligning large language models (LLMs) to human preferences, but gathering high quality human preference labels is a key bottleneck. We conduct a head-to-head comparison of RLHF vs. RL from AI Feedback (RLAIF) - a technique where preferences are labeled by an off-the-shelf LLM in lieu of humans, and we find that they result in similar improvements. On the task of summarization, human evaluators prefer generations from both RLAIF and RLHF over a baseline supervised fine-tuned model in ~70% of cases. Furthermore, when asked to rate RLAIF vs. RLHF summaries, humans prefer both at equal rates. These results suggest that RLAIF can yield human-level performance, offering a potential solution to the scalability limitations of RLHF

Scalable Generation of Universal Platelets from Human Induced Pluripotent Stem Cells

Summary Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid “surge” capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the β2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness

NO SPACE LEFT BEHIND - Graduate Urban Design Studio - LANDARCH 606

The following report documents the work of the 2015 Spring Graduate Urban Design Studio course in the Department of Landscape Architecture and Regional Planning. This fourteen week studio focused on using tactical urbanism to engage Springfield’s Metro Center neighborhood with visions to revitalize the downtown core of this legacy city. In addition to completing the components of a traditional urban design studio (site analyses, schematic plans, spatial designs, and programming), the student teams also developed conceptual projects to immediately engage the public. These efforts culminated in a free afternoon walking tour throughout the Metro Center that presented several tactical interventions. These interactive, public installations illustrated potential future initiatives and brought attention to overlooked areas and assets. Throughout the semester the teams were challenged to continuously consider both the short-term impacts of their interventions and the long-term visions for the future of Springfield’s urban core. This strategy allowed students to develop a process-based approach to urban design. It provided opportunities to engage stakeholders and test new ideas with the public, rather than simply creating a master plan without any real world interactions with the city and its populace. STUDIO GOALS • To enliven public space in Springfield’s Metro Center through small-scale urban design interventions which illustrate and inform long-term plans • To activate residual spaces in the downtown with Tactical Urbanism By matching long-term visions for the Metro Center with short-term, site-specific tactical interventions the teams were able to deliver a variety of ideas in multiple formats. Furthermore, the experience of interacting with community members during the installation of projects added a great deal of meaning to the research and design process. The work explores a community service learning strategy within the framework of an urban design studio with the goal of revitalizing the city of Springfield, Massachusetts, through sustainable design, planning, and engagement with the community. The six design-team interventions are documented and published as team-authored videos: 1. Union Station Green Corridor Maozhu Mao, Yuqing Wu https://www.youtube.com/watch?v=EnE8Yt8x0Es&feature=youtu.be 2. (No) Vacancy Chris Counihan, Michalagh Stoddard, Ruoying Tang https://youtu.be/CapaQ9gDxeM 3. Extra Space, Active Street Yu Yu https://youtu.be/2pgYq5HLNHA 4. Spring into Art Emilie Jordao, Matt Hisle, Jing Wang https://youtu.be/Vf2yk6Se6rU 5. Urban Agua Kellie Fenton, James Prendergast, Nelle Ward https://www.youtube.com/watch?v=vk2PUJMdhTU&feature=youtu.be 6. Make the Connection Yue Li, Yanhua Lu, Yi Yang https://youtu.be/EvQD0QYV97

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

A Bayesian analysis of pentaquark signals from CLAS data

We examine the results of two measurements by the CLAS collaboration, one of which claimed evidence for a $\Theta^{+}$ pentaquark, whilst the other found no such evidence. The unique feature of these two experiments was that they were performed with the same experimental setup. Using a Bayesian analysis we find that the results of the two experiments are in fact compatible with each other, but that the first measurement did not contain sufficient information to determine unambiguously the existence of a $\Theta^{+}$. Further, we suggest a means by which the existence of a new candidate particle can be tested in a rigorous manner.Comment: 5 pages, 3 figure

Search for the Θ+\Theta^+ pentaquark in the reaction γd→pK−K+n\gamma d \to p K^- K^+ n

A search for the \thp in the reaction $\gamma d \to pK^-K^+n$ was completed using the CLAS detector at Jefferson Lab. A study of the same reaction, published earlier, reported the observation of a narrow \thp resonance. The present experiment, with more than 30 times the integrated luminosity of our earlier measurement, does not show any evidence for a narrow pentaquark resonance. The angle-integrated upper limit on \thp production in the mass range of 1.52 to 1.56 GeV/c$^2$ for the $\gamma d \to pK^-\Theta^+$ reaction is 0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and angular distribution of \thp production. Using \lamstar production as an empirical measure of rescattering in the deuteron, the cross section upper limit for the elementary $\gamma n \to K^-\Theta^+$ reaction is estimated to be a factor of 10 higher, {\it i.e.}, $\sim 3$ nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment

Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure