37 research outputs found
Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells
No full textSummaryOne of the goals of synthetic biology is to develop programmable artificial gene networks that can transduce multiple endogenous molecular cues to precisely control cell behavior. Realizing this vision requires interfacing natural molecular inputs with synthetic components that generate functional molecular outputs. Interfacing synthetic circuits with endogenous mammalian transcription factors has been particularly difficult. Here, we describe a systematic approach that enables integration and transduction of multiple mammalian transcription factor inputs by a synthetic network. The approach is facilitated by a proportional amplifier sensor based on synergistic positive autoregulation. The circuits efficiently transduce endogenous transcription factor levels into RNAi, transcriptional transactivation, and site-specific recombination. They also enable AND logic between pairs of arbitrary transcription factors. The results establish a framework for developing synthetic gene networks that interface with cellular processes through transcriptional regulators
Morphisms between complete Riemannian pseudogroups
No full textAbstractWe introduce the concept of morphism of pseudogroups generalizing the étalé morphisms of Haefliger. With our definition, any continuous foliated map induces a morphism between the corresponding holonomy pseudogroups. The main theorem states that any morphism between complete Riemannian pseudogroups is complete, has a closure and its maps are C∞ along the orbit closures. Here, completeness and closure are versions for morphisms of concepts introduced by Haefliger for pseudogroups. This result is applied to approximate foliated maps by smooth ones in the case of transversely complete Riemannian foliations, yielding the foliated homotopy invariance of their spectral sequence. This generalizes the topological invariance of their basic cohomology, shown by El Kacimi-Alaoui–Nicolau. A different proof of the spectral sequence invariance was also given by the second author
The rational classification of links of codimension > 2
No full textLet m and p1,.,pr < m - 2 be positive integers. The set of links of codimension > 2, Em(∐k=1 rSPk), is the set of smooth isotopy classes of smooth embeddings ∐k=1 rSPk → Sm. Haefliger showed that Em(∐k=1 rSPk) is a finitely generated abelian group with respect to embedded connected summation and computed its rank in the case of knots, i.e. r = 1. For r > 1 and for restrictions on p1,.,pr the rank of this group can be computed using results of Haefliger or Nezhinsky. Our main result determines the rank of the group Em(∐k=1 rSPk) in general. In particular we determine precisely when Em(∐k=1 rSPk) is finite. We also accomplish these tasks for framed links. Our proofs are based on the Haefliger exact sequence for groups of links and the theory of Lie algebras. © de Gruyter 2014.The third author was supported in part by INTAS grant 06-1000014-6277, Moebius Contest Foundation for Young Scientists and Euler Foundation
Embeddings and immersions
No full textThis book covers fundamental techniques in the theory of C^{\infty }-imbeddings and C^{\infty }-immersions, emphasizing clear intuitive understanding and containing many figures and diagrams. Adachi starts with an introduction to the work of Whitney and of Haefliger on C^{\infty }-imbeddings and C^{\infty }-manifolds. The Smale-Hirsch theorem is presented as a generalization of the classification of C^{\infty }-imbeddings by isotopy and is extended by Gromov's work on the subject, including Gromov's convex integration theory. Finally, as an application of Gromov's work, the author introduces Haefliger's classification theorem of foliations on open manifolds. Also described here is the Adachi's work with Landweber on the integrability of almost complex structures on open manifolds. This book would be an excellent text for upper-division undergraduate or graduate courses
Precision multidimensional assay for high-throughput microRNA drug discovery
No full textISSN:2041-172
Mixed Erdheim-Chester disease with thoraco-abdominal involvement
No full textErdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. Mixed ECD-Langerhans cell histiocytosis (LCH) is uncommon, with fewer than 200 cases reported. Diagnosis is challenging and relies on clinical, radiological, and histopathological correlation. We present the case of a 61-year-old man with night sweats, weight loss, and recently diagnosed type 2 diabetes. Imaging revealed cystic lung lesions, perirenal infiltration, and circumferential aortic wall thickening. FDG PET-CT demonstrated multifocal hypermetabolism involving lymph nodes, perirenal soft tissues, and the aortic wall, but no bone involvement. These lesions were shown to progress on subsequent imaging. A lymph node and perirenal biopsies confirmed a mixed form of ECD-LCH with BRAFV600 E mutation and associated chronic myelomonocytic leukemia. The patient was started on targeted therapy with cobimetinib, a MEK inhibitor. Mixed ECD-LCH is a rare entity that typically demonstrates more frequent and widespread organ involvement, particularly affecting the lungs. Its clinical and radiological presentation can have features of both disorders, such as bone, lung, kidney, and vascular involvement. The diagnosis is challenging and requires biopsy with histopathology and genetic testing to be confirmed. Treatment is generally targeted therapy guided by the driver mutations that are identified. We present a rare case of mixed ECD-LCH with thoraco-abdominal and pulmonary involvement. Comprehensive diagnostic workup including histopathology and molecular profiling is crucial for accurate diagnosis and initiation of targeted therapy.
© The Author(s) 2025
Embeddability of Simplicial Complexes is Undecidable
No full textWe consider the following decision problem EMBEDk→d in computational topology (where k ≤ d are fixed positive integers): Given a finite simplicial complex K of dimension k, does there exist a (piecewise-linear) embedding of K into ℝd?
The special case EMBED1→2 is graph planarity, which is decidable in linear time, as shown by Hopcroft and Tarjan. In higher dimensions, EMBED2→3 and EMBED3→3 are known to be decidable (as well as NP-hard), and recent results of Čadek et al. in computational homotopy theory, in combination with the classical Haefliger–Weber theorem in geometric topology, imply that EMBEDk→d can be solved in polynomial time for any fixed pair (k, d) of dimensions in the so-called metastable range .
Here, by contrast, we prove that EMBEDk→d is algorithmically undecidable for almost all pairs of dimensions outside the metastable range, namely for . This almost completely resolves the decidability vs. undecidability of EMBEDk→d in higher dimensions and establishes a sharp dichotomy between polynomial-time solvability and undecidability.
Our result complements (and in a wide range of dimensions strengthens) earlier results of Matoušek, Tancer, and the second author, who showed that EMBEDk→d is undecidable for 4 ≤ k ϵ {d – 1, d}, and NP-hard for all remaining pairs (k, d) outside the metastable range and satisfying d ≥ 4
Classification of knotted tori in 2-metastable dimension
No full textThis paper is devoted to the classical Knotting Problem: for a given manifold N and number m describe the set of isotopy classes of embeddings N → Sm. We study the specific case of knotted tori, that is, the embeddings Sp × Sq → Sm. The classification of knotted tori up to isotopy in the metastable dimension range m > p + 3 2 q + 2, p 6 q, was given by Haefliger, Zeeman and A. Skopenkov. We consider the dimensions below the metastable range and give an explicit criterion for the finiteness of this set of isotopy classes in the 2-metastable dimension: Theorem. Assume that p+ 4 3 q +2 2p+q +2. Then the set of isotopy classes of smooth embeddings Sp × Sq → Sm is infinite if and only if either q + 1 or p + q + 1 is divisible by 4. © 2012 RAS(DoM) and LMS.The first and second authors were supported in part by the Slovenian Research Agency (grant nos. P1-0292-0101 and J1-4144-0101). The third author was supported in part by the Russian Foundation for Basic Research (grant no. 12-01-00748-a), the Programme of the President of the Russian Federation for the Support of Young Scientists (grant no. MK-3965.2012.1), the "Dynasty" Foundation and the Simons Foundation
Using Glittr.org to find, compare and re-use online materials for training and education.
No full textA wealth of excellent training and educational materials for the computational life sciences are scattered around the Internet, but they can be hard to find. Many materials reside in public Git repositories that are hosted on platforms such as GitHub and GitLab. Glittr.org is a manually curated database of Git repositories, which enables users to find educational materials that would otherwise be hard to identify. With the application, users can search and compare educational materials based on topic and author, but also on engagement metrics such as stargazers (bookmarks) and recency (days since last commit). Glittr.org currently contains 664 entries, which are assigned to six different categories within the domain of computational life sciences. By analysing the database, we reveal insights in the availability of materials per topic, collaboration patterns of developers, and licensing practices. This knowledge helps to understand in which areas open educational materials are scant, the importance of Git for collaboration on educational materials and how licensing can be improved to enhance sharing and reuse. Taken together, we show that Glittr.org contains a wealth of connected and openly available metadata. Therefore, it enhances adherence to the FAIR (Findable, Accessible, Interoperable, Reusable) principles, which benefits learners, teachers and trainers in the entire life sciences community and beyond
