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American Association for the Advancement of Science (AAAS)
Publication Date: 2014-10-25
Description: Cellular circuits sense the environment, process signals, and compute decisions using networks of interacting proteins. To model such a system, the abundance of each activated protein species can be described as a stochastic function of the abundance of other proteins. High-dimensional single-cell technologies, such as mass cytometry, offer an opportunity to characterize signaling circuit-wide. However, the challenge of developing and applying computational approaches to interpret such complex data remains. Here, we developed computational methods, based on established statistical concepts, to characterize signaling network relationships by quantifying the strengths of network edges and deriving signaling response functions. In comparing signaling between naive and antigen-exposed CD4(+) T lymphocytes, we find that although these two cell subtypes had similarly wired networks, naive cells transmitted more information along a key signaling cascade than did antigen-exposed cells. We validated our characterization on mice lacking the extracellular-regulated mitogen-activated protein kinase (MAPK) ERK2, which showed stronger influence of pERK on pS6 (phosphorylated-ribosomal protein S6), in naive cells as compared with antigen-exposed cells, as predicted. We demonstrate that by using cell-to-cell variation inherent in single-cell data, we can derive response functions underlying molecular circuits and drive the understanding of how cells process signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334155/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334155/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krishnaswamy, Smita -- Spitzer, Matthew H -- Mingueneau, Michael -- Bendall, Sean C -- Litvin, Oren -- Stone, Erica -- Pe'er, Dana -- Nolan, Garry P -- 1K01DK095008/DK/NIDDK NIH HHS/ -- 1R01CA130826/CA/NCI NIH HHS/ -- 1U54CA121852-01A1/CA/NCI NIH HHS/ -- CA 09-011/CA/NCI NIH HHS/ -- HHSN268201000034C/HV/NHLBI NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HV-10-05/HV/NHLBI NIH HHS/ -- K01 DK095008/DK/NIDDK NIH HHS/ -- P01 CA034233/CA/NCI NIH HHS/ -- R00 GM104148/GM/NIGMS NIH HHS/ -- R01 CA130826/CA/NCI NIH HHS/ -- S10RR027582-01/RR/NCRR NIH HHS/ -- U19 AI057229/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 CA149145/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1250689. doi: 10.1126/science.1250689. Epub 2014 Oct 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY, USA. ; Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA. ; Molecular Biology Section, Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. ; Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY, USA. dpeer@biology.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342659" target="_blank"〉PubMed〈/a〉
Keywords: Animals ; CD4-Positive T-Lymphocytes/*immunology ; Computer Simulation ; Image Cytometry ; Male ; Mice ; Mice, Mutant Strains ; Mitogen-Activated Protein Kinase 1/genetics ; Receptors, Antigen, T-Cell/*metabolism ; Ribosomal Protein S6/metabolism ; Signal Transduction ; Single-Cell Analysis/*methods ; Systems Biology/*methods ; eIF-2 Kinase/metabolism
Print ISSN: 0036-8075
Electronic ISSN: 1095-9203
Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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• 2
Electronic Resource
Springer
Semiconductors 34 (2000), S. 1128-1132
ISSN: 1063-7826
Source: Springer Online Journal Archives 1860-2000
Topics: Electrical Engineering, Measurement and Control Technology , Physics
Notes: Abstract For the first time, ZnS:Cu films with an intense photoluminescence were prepared by a chemical nonvacuum method. They were produced by means of the combined pyrolytic deposition of zinc and copper dithiocarbamates onto glass and ceramic substrates heated up to 260–300°C. A close packing of practically identical grains is characteristic of these films, with grain sizes depending on the substrate type. The photoluminescence and electroluminescence spectra include the blue, green, and yellow bands typical of copper. The band-intensity ratio depends on the film-preparation conditions, as well as on their excitation, which makes it possible to change the emission color of radiators in a wide range (from blue to white).
Type of Medium: Electronic Resource
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• 3
Electronic Resource
Springer
Ukrainian mathematical journal 37 (1985), S. 408-412
ISSN: 1573-9376
Source: Springer Online Journal Archives 1860-2000
Topics: Mathematics
Type of Medium: Electronic Resource
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• 4
Electronic Resource
Springer
Ukrainian mathematical journal 42 (1990), S. 1452-1461
ISSN: 1573-9376
Source: Springer Online Journal Archives 1860-2000
Topics: Mathematics
Notes: Abstract An algorithm for constructing the operator OMn({ϕkx}; x, y) with the properties $$\begin{gathered} O_{Mn} (\{ \varphi _{ks} \} ;x,y) \in C^r (R^2 \backslash G), G = \{ \Gamma _k \cap \Gamma _l ;k, l = 1, M;k \ne l\} , r 〉 n, \hfill \\ \frac{{\partial ^n O_{Mn} (\{ \varphi _{ks} \} ;x,y)}}{{\partial v_a^p }}|_{\Gamma _a } = \varphi _{ap} (x,y)|_{\Gamma _Q '} q = \overline {1, M} ; p = \overline {0, n,} \hfill \\ \end{gathered}$$ , is proposed for the first time; here {г g } is a given family of straight lines of an arbitrary location, νq is a normal to гq, ϕqqp(x, y) ∈ Cr−P(R2), $$p = \overline {0, n,}$$ , are given functions. An integral analog of the generalized D'Alembert formula, which utilizes averaging certain repeated integrals of traces rather than the traces themselves, serves as the basis for this paper. An integral representation of the remainder of approximating functions u(x, y) ∈ Cr(R2) with properties by the operators OMn({ϕ ks }; x, y).
Type of Medium: Electronic Resource
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• 5
Electronic Resource
Springer
Neuroscience and behavioral physiology 30 (2000), S. 671-678
ISSN: 1573-899X
Source: Springer Online Journal Archives 1860-2000
Topics: Biology , Medicine
Notes: Abstract According to current concepts, memory can be disrupted by administration of protein synthesis inhibitors over a relatively short time period before and after learning. However, data have been obtained indicating that protein synthesis inhibitors can induce amnesia when given long after learning if administration is performed in reminder conditions, i.e., when the animal is presented with one of the environmental components which previously formed the learning situation. The aim of the present work was to confirm the possibility of inducing memory disruption in chicks at late post–learning stages by administering the protein synthesis inhibitor cycloheximide in association with a reminder procedure. Day–old chicks were trained to perform a standard passive avoidance task. Chicks were given cycloheximide (20 μg, intracerebrally) 5 min before the reminder procedure, which was performed 2, 24, or 48 h after training. Testing was conducted 0.5, 1, 3, 24, and 48 h after the reminder. Administration of cycloheximide in association with the reminder procedure induced the development of temporary amnesia, whose duration gradually decreased as the interval between training and reminding increased. These data led to the hypothesis that a memory reactivated by a reminder undergoes a process of reorganization and reconsolidation, which depends on the synthesis of new proteins. The quenching of the ability of protein synthesis inhibition during the reminder to disrupt memory demonstrates the existence of a gradual process resulting in consolidation of memory between 2 and 48 h of learning.
Type of Medium: Electronic Resource
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• 6
Electronic Resource
Springer
Ukrainian mathematical journal 24 (1972), S. 197-202
ISSN: 1573-9376
Source: Springer Online Journal Archives 1860-2000
Topics: Mathematics
Type of Medium: Electronic Resource
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• 7
Electronic Resource
Springer
Ukrainian mathematical journal 25 (1973), S. 538-544
ISSN: 1573-9376
Source: Springer Online Journal Archives 1860-2000
Topics: Mathematics
Type of Medium: Electronic Resource
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• 8
Electronic Resource
Springer
Ukrainian mathematical journal 28 (1976), S. 624-629
ISSN: 1573-9376
Source: Springer Online Journal Archives 1860-2000
Topics: Mathematics
Type of Medium: Electronic Resource
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• 9
Electronic Resource
Springer
Ukrainian mathematical journal 41 (1989), S. 986-990
ISSN: 1573-9376
Source: Springer Online Journal Archives 1860-2000
Topics: Mathematics
Type of Medium: Electronic Resource
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• 10
Electronic Resource
Springer
Ukrainian mathematical journal 44 (1992), S. 1378-1384
ISSN: 1573-9376
Source: Springer Online Journal Archives 1860-2000
Topics: Mathematics
Notes: Abstract A general algorithm is proposed for constructing interlineation operators $$\bar O_{MN} f(x)$$ , x=(x1, x2) with the properties $$\begin{array}{*{20}c} {\left. {\frac{{\partial ^s \bar O_{MN} f}}{{\partial v_k^s }}} \right|_{\Gamma _k } = \left. {\frac{{\partial ^s f}}{{\partial v_k^s }}} \right|_{\Gamma _k } = \left. {\varphi _{ks} (x)} \right|_{\Gamma _k } ,k = \overline {1,M;} s = \overline {0,N} ,} \\ {\bar O_{MN} x^\alpha \equiv x^\alpha ,0 \leqslant |\alpha | = \alpha _1 + \alpha _2 \leqslant M(N + 1) - 1, x^\alpha = x_1^{\alpha _1 } x_2^{\alpha _2 } ,} \\ \end{array}$$ where {γk} is a given set of lines of arbitrary disposition on the plane Ox1x2,Ν k ⊥ γk. An integral representation is derived of the residual of approximation of the function f(x) by the operators $$\bar O_{MN} f(x)$$ . Examples are considered of interlineation operators preserving the class Cr(R2), and also operators not preserving the differentiability class, to which the function f(x) belongs.
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