Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons

Recent studies show that combinations of defined key developmental transcription factors (TFs) can reprogram somatic cells to pluripotency or induce cell conversion of one somatic cell type to another. However, it is not clear if single genes can define a cell̀s identity and if the cell fate defining potential of TFs is also operative in pluripotent stem cells in vitro. Here, we show that ectopic expression of the neural TF Neurogenin2 (Ngn2) is sufficient to induce rapid and efficient differentiation of embryonic stem cells (ESCs) into mature glutamatergic neurons. Ngn2-induced neuronal differentiation did not require any additional external or internal factors and occurred even under pluripotency-promoting conditions. Differentiated cells displayed neuron-specific morphology, protein expression, and functional features, most importantly the generation of action potentials and contacts with hippocampal neurons. Gene expression analyses revealed that Ngn2-induced in vitro differentiation partially resembled neurogenesis in vivo, as it included specific activation of Ngn2 target genes and interaction partners. These findings demonstrate that a single gene is sufficient to determine cell fate decisions of uncommitted stem cells thus giving insights into the role of key developmental genes during lineage commitment. Furthermore, we present a promising tool to improve directed differentiation strategies for applications in both stem cell research and regenerative medicine

Tifig

In 2014, Apple introduced a new programming language called Swift which replaced Objective-C as the default programming language to develop applications for Apple's platforms. Since then, the language has evolved a lot and was open-sourced at the end of 2015. There are now official releases for both macOS and Ubuntu and there are efforts from the community to bring the language to other platforms as well. With its Xcode IDE (integrated development environment) Apple focuses mainly on the development of iOS and macOS apps. However, Xcode is not available on platforms other than the Mac and there aren't a lot of alternatives yet. Additionally, many programmers are interested in using Swift for other areas such as web development. The main goal of this project is to create a cross-platform Swift IDE based on Eclipse which contains the basic components required to develop Swift programs. Over the course of the term project a simple Swift IDE called Tifig has been developed. The user can edit source files, build projects and run the resulting executables all from within the IDE. Every time the user changes a source file, the code is re-parsed and syntax errors are reported in the form of markers in the editor. In the subsequent master thesis the parser has been further improved and updated for Swift 3. Additionally, an indexer has been implemented. The semantic knowledge that is obtained by the indexer allowed for the development of the code navigation features "Open Type" and "Jump to Definition". A lot of Swift's core types and operators are not part of the language itself, but are instead declared in the standard library. For this reason, Tifig also indexes the standard library and makes its public symbols available in each project

Tifig

In 2014, Apple introduced a new programming language called Swift which replaced Objective-C as the default programming language to develop applications for Apple's platforms. Since then, the language has evolved a lot and was open-sourced at the end of 2015. There are now official releases for both macOS and Ubuntu and there are efforts from the community to bring the language to other platforms as well. With its Xcode IDE (integrated development environment) Apple focuses mainly on the development of iOS and macOS apps. However, Xcode is not available on platforms other than the Mac and there aren't a lot of alternatives yet. Additionally, many programmers are interested in using Swift for other areas such as web development. The main goal of this project is to create a cross-platform Swift IDE based on Eclipse which contains the basic components required to develop Swift programs. Over the course of the term project a simple Swift IDE called Tifig has been developed. The user can edit source files, build projects and run the resulting executables all from within the IDE. Every time the user changes a source file, the code is re-parsed and syntax errors are reported in the form of markers in the editor. In the subsequent master thesis the parser has been further improved and updated for Swift 3. Additionally, an indexer has been implemented. The semantic knowledge that is obtained by the indexer allowed for the development of the code navigation features "Open Type" and "Jump to Definition". A lot of Swift's core types and operators are not part of the language itself, but are instead declared in the standard library. For this reason, Tifig also indexes the standard library and makes its public symbols available in each project

CharWars Rise of the fallen strings: Replace C-String Library calls with C++ std::string Operations

C strings are still in heavy use in C++ programs. Additionally, standardized C functions such as strcpy() and strstr() are often used to modify or analyze the content of the strings. Unfortunately, because of the fact that a C string is just a pointer to a zero-terminated character array, those functions have a lot of drawbacks regarding performance, safety and readability. The std::string class from the C++ standard library and its member functions provide a lot of the same functionality without these downsides. Building on previous work from our term project Pointerminator we extended the existing Eclipse CDT plug-in so that it helps a programmer to find and automatically refactor pieces of code, that use C strings in an unfavourable way. We started with an analysis of the various ways C strings and their related C functions are used in practice. Based on that analysis we defined possible refactorings for a subset of the standardized C string functions. We then added this functionality to the existing plug-in, wrote corresponding unit tests and documented its architecture. Finally, we tested the plug-in in the code base of an open source C++ application called XBMC. The results of these tests allowed us to optimize the plug-in and to fix some of the problems that we discovered during testing

Pointerminator

Pointers and Arrays as inherited from C are still in heavy use in C++ programs. They are used to represent strings, arrays, objects on the heap or they appear in function signatures to do call-by-reference. However, issues like resource responsibility, degradation of an array to a pointer loosing its dimension or zero termination of byte sequences lead to poor quality and potential security problems. Modern C++ and its standard library provide a lot of functionality to avoid the use of raw pointers and arrays. If those concepts are applied correctly, they can lead to much better and more maintainable code. The goal of our term project is to write a plug-in for Eclipse CDT that allows a programmer to find and automatically refactor pieces of code, that use pointers in an unfavourable way. We started with an analysis of the various roles pointers can have. Based on that analysis we decided that the plug-in should be able to refactor C strings, C arrays and pointer parameters. Then we implemented the plug-in and documented its architecture. Finally, we tested the plug-in in the code base of an existing C++ application called fish shell. The results of these tests allowed us to optimize the plug-in and to fix some of the problems that we discovered during testing

Inferring single-cell gene expression mechanisms using stochastic simulation.

MotivationStochastic promoter switching between transcriptionally active (ON) and inactive (OFF) states is a major source of noise in gene expression. It is often implicitly assumed that transitions between promoter states are memoryless, i.e. promoters spend an exponentially distributed time interval in each of the two states. However, increasing evidence suggests that promoter ON/OFF times can be non-exponential, hinting at more complex transcriptional regulatory architectures. Given the essential role of gene expression in all cellular functions, efficient computational techniques for characterizing promoter architectures are critically needed.ResultsWe have developed a novel model reduction for promoters with arbitrary numbers of ON and OFF states, allowing us to approximate complex promoter switching behavior with Weibull-distributed ON/OFF times. Using this model reduction, we created bursty Monte Carlo expectation-maximization with modified cross-entropy method ('bursty MCEM(2)'), an efficient parameter estimation and model selection technique for inferring the number and configuration of promoter states from single-cell gene expression data. Application of bursty MCEM(2) to data from the endogenous mouse glutaminase promoter reveals nearly deterministic promoter OFF times, consistent with a multi-step activation mechanism consisting of 10 or more inactive states. Our novel approach to modeling promoter fluctuations together with bursty MCEM(2) provides powerful tools for characterizing transcriptional bursting across genes under different environmental conditions.Availability and implementationR source code implementing bursty MCEM(2) is available upon [email protected] informationSupplementary data are available at Bioinformatics online

Hydrogen-impurity induced unconventional magnetism in semiconducting molybdenum ditelluride

Layered transition-metal dichalcogenides are proposed as building blocks for van der Waals (vdW) heterostructures due to their graphene-like two dimensional structure. For this purpose, a magnetic semiconductor could represent an invaluable component for various spintronics and topotronics devices. Here, we combine different local magnetic probe spectroscopies with angle-resolved photoemission and density-functional theory calculations to show that 2H-MoTe2 is on the verge of becoming magnetic. Our results present clear evidence that the magnetism can be "switched on" by a hydrogen-like impurity. We also show that this magnetic state survives up to the free surface region, demonstrating the material's potential applicability as a magnetic component for thin-film heterostructures.Comment: 17 pages, 13 figures, including supplementar