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The cool stuff in Premiere Pro : learn advanced editing techniques to dramatically speed up your workflow
Gain in-depth knowledge of Premiere Pro, and learn how the software \"thinks.\" You'll acquire new skills that will help you choose the best workflow for your project, and simplify and accelerate your video editing process. Learn how you can edit a lot faster with smarter workflows that automate several steps in the editing process. You'll also see how custom settings, presets, keyboard shortcuts and templates saves hours of work. By tailoring the software to your needs you save clicks on just about every task. With many traditional jobs now being done by one person, its important to understand audio smoothing, color grading, motion graphics, and advanced editing techniques. You'll learn these skills and disciplines and see how they'll enhance your project's workflow. All the authors are professional editors and want to know exactly how to cut your film as fast as possible with top quality output. There is invaluable information in The Cool Stuff in Premiere Pro that's not available anywhere else - not even in Adobe's own manuals.
Book
KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks
Cell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors, as is exemplified by reprogramming somatic cells to pluripotent stem cells through the expression of OCT4, KLF4, SOX2 and cMYC. How transcription factors orchestrate the complex molecular changes around their target gene loci remains incompletely understood. Here, using KLF4 as a paradigm, we provide a transcription-factor-centric view of chromatin reorganization and its association with three-dimensional enhancer rewiring and transcriptional changes during the reprogramming of mouse embryonic fibroblasts to pluripotent stem cells. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in enhancer connectivity, whereas disruption of individual KLF4 binding sites within pluripotent-stem-cell-specific enhancers was sufficient to impair enhancer–promoter contacts and reduce the expression of associated genes. Our study provides an integrative view of the complex activities of a lineage-specifying transcription factor and offers novel insights into the nature of the molecular events that follow transcription factor binding.
Di Giammartino, Kloetgen, Polyzos, Liu et al. probe chromatin organization, enhancer status and transcriptional changes and show that KLF4 acts as a transcriptional regulator and chromatin organizer during induced pluripotent stem cell reprogramming and in pluripotent stem cells.
Journal Article
Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear enhancer gene regulatory activity during cell state transitions
Comprehensive enhancer discovery is challenging because most enhancers, especially those contributing to complex diseases, have weak effects on gene expression. Our gene regulatory network modeling identified that nonlinear enhancer gene regulation during cell state transitions can be leveraged to improve the sensitivity of enhancer discovery. Using human embryonic stem cell definitive endoderm differentiation as a dynamic transition system, we conducted a mid-transition CRISPRi-based enhancer screen. We discovered a comprehensive set of enhancers for each of the core endoderm-specifying transcription factors. Many enhancers had strong effects mid-transition but weak effects post-transition, consistent with the nonlinear temporal responses to enhancer perturbation predicted by the modeling. Integrating three-dimensional genomic information, we were able to develop a CTCF-loop-constrained Interaction Activity model that can better predict functional enhancers compared to models that rely on Hi-C-based enhancer–promoter contact frequency. Our study provides generalizable strategies for sensitive and systematic enhancer discovery in both normal and pathological cell state transitions.
CRISPRi-based screen identifies enhancers that nonlinearly regulate lineage-specifying transcription factors during definitive endoderm differentiation. A new CTCF-loop-constrained Interaction Activity (CIA) model is better at predicting functional enhancers than previous Hi-C-based enhancer–promoter contact frequency models.
Journal Article
The Role of 3D Regulatory Enhancer Landscapes and Enhancer Hubs in Stem Cell Fate Maintenance and Change
Mammalian embryogenesis begins with sequential cell fate decisions giving rise to three essential lineages, the trophectoderm (TE), the epiblast (EPI) and the primitive endoderm (PrE). Key signaling pathways and transcription factors controlling these early embryonic decisions have been identified, but the non-coding regulatory elements via which transcriptional regulators enact these fates remain understudied. We have characterized, at genome-wide scale, enhancer activity and connectivity in embryo-derived stem cell lines representing each early developmental fate, yielding high-resolution 2D and 3D regulatory maps of the first cell fate decisions. We observed extensive enhancer remodeling and fine-scale 3D chromatin rewiring among the three lineages, strongly associating with transcriptional changes. In each lin.age, high degree of connectivity or “hubness” positively correlates with levels and cell-type specificity of gene expression and enriches for essential genes. Genes within 3D hubs also show a significantly stronger probability of coregulation during cell fate transitions, compared to genes in linear proximity or within the same contact domains. By building and testing various computational models of transcriptional regulation; and including specific 3D chromatin features, we were able to outperform models using only 2D promoter or proximal variables in predicting cell-type specific gene expression. Genome-wide in silico perturbations allowed us to nominate candidate functional enhancers in each cell lineage for validation at several relevant genomic loci. Our study comprehensively identifies 3D regulatory hubs associated with the earliest mammalian lineages and describes their relationship to gene expression and cell identity, providing a framework to understand lineage-specific transcriptional behaviors.
Dissertation
3D Enhancer–promoter networks provide predictive features for gene expression and coregulation in early embryonic lineages
Mammalian embryogenesis commences with two pivotal and binary cell fate decisions that give rise to three essential lineages: the trophectoderm, the epiblast and the primitive endoderm. Although key signaling pathways and transcription factors that control these early embryonic decisions have been identified, the non-coding regulatory elements through which transcriptional regulators enact these fates remain understudied. Here, we characterize, at a genome-wide scale, enhancer activity and 3D connectivity in embryo-derived stem cell lines that represent each of the early developmental fates. We observe extensive enhancer remodeling and fine-scale 3D chromatin rewiring among the three lineages, which strongly associate with transcriptional changes, although distinct groups of genes are irresponsive to topological changes. In each lineage, a high degree of connectivity, or ‘hubness’, positively correlates with levels of gene expression and enriches for cell-type specific and essential genes. Genes within 3D hubs also show a significantly stronger probability of coregulation across lineages compared to genes in linear proximity or within the same contact domains. By incorporating 3D chromatin features, we build a predictive model for transcriptional regulation (3D-HiChAT) that outperforms models using only 1D promoter or proximal variables to predict levels and cell-type specificity of gene expression. Using 3D-HiChAT, we identify, in silico, candidate functional enhancers and hubs in each cell lineage, and with CRISPRi experiments, we validate several enhancers that control gene expression in their respective lineages. Our study identifies 3D regulatory hubs associated with the earliest mammalian lineages and describes their relationship to gene expression and cell identity, providing a framework to comprehensively understand lineage-specific transcriptional behaviors.
Here, the authors describe 3D hubs as regulatory subunits of gene expression in the three essential lineages of embryogenesis. They develop a computational model that can predict novel enhancers and they validate such enhancers in the context of specific lineages.
Journal Article
Additions for Jacobi Operators and the Toda Hierarchy of Lattice Equations
We develop a class of Darboux transformations called additions for Jacobi operators. We show that by conjugating by a reflection, an addition may be inverted by another addition with the same spectral parameter. This leads to the development of an “infinitesimal addition”, which allows the transformation to be interpreted as a vector field on a space of Jacobi operators rather than a discrete transformation. We show that in an appropriate limit, this vector field generates the flows of the Toda hierarchy of lattice equations, in analogy to the known fact that an infinitesimal addition on Schr¨odinger operators can generate the Korteweg-de Vries hierarchy of PDEs. Furthermore, in the case of scattering-type operators, the same vector field appears as a gradient of the transmission coefficient, indicating that the values of the transmission coefficent form a commuting family of functionals with respect to the Poisson bracket corresponding to the Toda hierarchy.
Dissertation
KLF4 is involved in the organization and regulation of pluripotency-associated 3D enhancer networks
Cell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors (TFs), as is exemplified by reprogramming somatic cells to pluripotent stem cells (PSCs) via expression of OCT4, KLF4, SOX2 and cMYC. How TFs orchestrate the complex molecular changes around their target gene loci remains incompletely understood. Here, using KLF4 as a paradigm, we provide a TF-centric view of chromatin reorganization and its association to 3D enhancer rewiring and transcriptional changes during reprogramming of mouse embryonic fibroblasts to PSCs. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in enhancer connectivity, while disruption of individual KLF4 binding sites within PSC-specific enhancers was sufficient to impair enhancer-promoter contacts and reduce expression of associated genes. Our study provides an integrative view of the complex activities of a lineage-specifying TF and offers novel insights into the nature of molecular events that follow TF binding.
Journal Article
Development of new technology for the improvement of a citizen science project: Clean Marine smartphone app
Marine debris can present a series of detrimental outcomes to South Carolina's coastal waters habitats, and species. Marine debris are manmade objects that have been discarded into the marine environment and can pose navigational hazards, increase water pollution by leaking fuel or other pollutants, trap coastal and estuarine species, and impair the aesthetics of a tidal marsh or estuary. One of the challenges to managing marine debris is timely, accurate, reporting. In 2011, the South Carolina Marine Debris Initiative was created. Led by various federal, state, and local regulatory agencies, the purpose of this initiative was to coordinate efforts to manage marine debris removal and to raise public awareness about the problem. As part of the Marine Debris Initiative, the National Office of Oceanic and Atmospheric Administration Office of Marine Debris awarded funding to state and local agencies which led to the creation of the Clean Marine Program. This program instructs volunteers in how to document the location of marine debris, properly complete a paper form while boating, and then digitally submit the data to a web form when back on land. The hypothesis of this thesis was that the current submission method could be simplified by developing an application for smartphones that performs all the functions of the paper/web form. The application developed allows users to immediately report the debris sighting using a quick and convenient electronic medium. The application was programmed for use on the Android operating system for smartphone handsets & tablet computers. Once the application was developed and tested, it was promoted via nationwide nautical groups alongside the Clean Marine Program. Questionnaires collected from willing anonymous participants were used to improve the application's usefulness. Based on questionnaire responses, debris submissions, and the app's market performance, it was successful in being more efficient and appealing way to submit debris.
Dissertation
A licence to lay blame
Professor Diane Ravitch, a historian of education and former US assistant secretary of education, explained in a 2010 article for The Wall Street Journal why she was opposed to blaming teachers for the problems of America's education system: \"The current emphasis on accountability has created a punitive atmosphere in the schools. Fellow American education writer Alfie Kohn has similarly noted how politicians and the educational establishment express \"outrage\" at low academic achievement and believe in quick fixes such as blaming teachers.
Trade Publication Article