In theory, neurons modelled as single layer perceptrons can implement all linearly separable computations. In practice, however, these computations may require arbitrarily precise synaptic weights. ...This is a strong constraint since both biological neurons and their artificial counterparts have to cope with limited precision. Here, we explore how non-linear processing in dendrites helps overcome this constraint. We start by finding a class of computations which requires increasing precision with the number of inputs in a Perceptron and show that it can be implemented without this constraint in a neuron with sub-linear dendritic subunits. Then, we complement this analytical study by a simulation of a biophysical neuron model with two passive dendrites and a soma, and show that it can implement this computation. This work demonstrates a new role of dendrites in neural computation: by distributing the computation across independent subunits, the same computation can be performed more efficiently with less precise tuning of the synaptic weights. This work not only offers new insight into the importance of dendrites for biological neurons, but also paves the way for new, more efficient architectures of artificial neuromorphic chips.
A phasing algorithm for macromolecular crystallography is proposed that utilizes diffraction data from multiple crystal forms – crystals of the same molecule with different unit‐cell packings ...(different unit‐cell parameters or space‐group symmetries). The approach is based on the method of iterated projections, starting with no initial phase information. The practicality of the method is demonstrated by simulation using known structures that exist in multiple crystal forms, assuming some information on the molecular envelope and positional relationships between the molecules in the different unit cells. With incorporation of new or existing methods for determination of these parameters, the approach has potential as a method for ab initio phasing.
A phasing algorithm for protein crystallography using diffraction data from multiple crystal forms is proposed. The algorithm is evaluated by simulation, and practical aspects and potential for ab initio phasing are discussed.
Uniqueness of the phase problem in macromolecular crystallography, and its relationship to the case of single particle imaging, is considered. The crystallographic problem is characterized by a ...constraint ratio that depends only on the size and symmetry of the molecule and the unit cell. The results are used to evaluate the effect of various real‐space constraints. The case of an unknown molecular envelope is considered in detail. The results indicate the quite wide circumstances under which ab initio phasing should be possible.
In the critically acclaimedLa Fin de la Pauverté?, Romain D. Huret identifies a network of experts who were dedicated to the post-World War II battle against poverty in the United States. John ...Angell's translation of Huret's work brings to light for an English-speaking audience this critical set of intellectuals working in federal government, academic institutions, and think tanks. Their efforts to create a policy bureaucracy to support federal socio-economic action spanned from the last days of the New Deal to the late 1960s when President Richard M. Nixon implemented the Family Assistance Plan. Often toiling in obscurity, this cadre of experts waged their own war not only on poverty but on the American political establishment. Their policy recommendations, as Huret clearly shows, often militated against the unscientific prejudices and electoral calculations that ruled Washington D.C. politics.
The Experts' War on Povertyhighlights the metrics, research, and economic and social facts these social scientists employed in their work, and thereby reveals the unstable institutional foundation of successive executive efforts to grapple with gross social and economic disparities in the United States. Huret argues that this internal war, coming at a time of great disruption due to the Cold War, undermined and fractured the institutional system officially directed at ending poverty. The official War on Poverty, which arguably reached its peak under President Lyndon B. Johnson, was thus fomented and maintained by a group of experts determined to fight poverty in radical ways that outstripped both the operational capacity of the federal government and the political will of a succession of presidents.
Properties of the phase problem for two‐dimensional crystals are examined. This problem is relevant to protein structure determination using diffraction from two‐dimensional crystals that has been ...proposed using new X‐ray free‐electron laser sources. The problem is shown to be better determined than for conventional three‐dimensional crystallography, but there are still a large number of solutions in the absence of additional a priori information. Molecular envelope information reduces the size of the solution set, and for an envelope that deviates sufficiently from the unit cell a unique solution is possible. The effects of various molecular surface features and incomplete data on uniqueness and prospects for ab initio phasing are assessed. Simulations of phase retrieval for two‐dimensional crystal data are described in the second paper in this series.
Properties of the phase problem for two‐dimensional crystals are examined. Implications for ab initio phasing of X‐ray free‐electron laser data from two‐dimensional crystalline specimens are described.
Background & Aims ZBP-89 (also ZNF148 or Zfp148) is a butyrate-inducible zinc finger transcription factor that binds to GC-rich DNA elements. Deletion of the N-terminal domain is sufficient to ...increase mucosal susceptibility to chemical injury and inflammation. We investigated whether conditional deletion of ZBP-89 from the intestinal and colonic epithelium of mice increases their susceptibility to pathogens such as Salmonella typhimurium. Methods We generated mice with a conditional null allele of Zfp148 (ZBP-89FL/FL ) using homologous recombination to flank Zfp148 with LoxP sites (ZBP-89FL/FL ), and then bred the resulting mice with those that express VillinCre. We used microarray analysis to compare gene expression patterns in colonic mucosa between ZBP-89ΔInt and C57BL/6 wild-type mice (controls). Mice were gavaged with 2 isogenic strains of S typhimurium after administration of streptomycin. Results Microarray analysis revealed that the colonic mucosa of ZBP-89ΔInt mice had reduced levels of tryptophan hydroxylase 1 (Tph1) messenger RNA, encoding the rate-limiting enzyme in enterochromaffin cell serotonin (5-hydroxytryptamine 5HT) biosynthesis. DNA affinity precipitation demonstrated direct binding of ZBP-89 to the mouse Tph1 promoter, which was required for its basal and butyrate-inducible expression. ZBP-89ΔInt mice did not increase mucosal levels of 5HT in response to S typhimurium infection, and succumbed to the infection 2 days before control mice. The ΔhilA isogenic mutant of S typhimurium lacks this butyrate-regulated locus and stimulated, rather than suppressed, expression of Tph1 approximately 50-fold in control, but not ZBP-89ΔInt , mice, correlating with fecal levels of butyrate. Conclusions ZBP-89 is required for butyrate-induced expression of the Tph1 gene and subsequent production of 5HT in response to bacterial infection in mice. Reductions in epithelial ZBP-89 increase susceptibility to colitis and sepsis after infection with S typhimurium , partly because of reduced induction of 5HT production in response to butyrate and decreased secretion of antimicrobial peptides.
The phase problem for two‐dimensional crystals. II. Simulations Arnal, Romain D.; Zhao, Yun; Mitra, Alok K. ...
Acta crystallographica. Section A, Foundations and advances,
September 2018, 2018-Sep-01, 2018-09-01, 20180901, Letnik:
74, Številka:
5
Journal Article
Recenzirano
Phasing of diffraction data from two‐dimensional crystals using only minimal molecular envelope information is investigated by simulation. Two‐dimensional crystals are an attractive target for ...studying membrane proteins using X‐ray free‐electron lasers, particularly for dynamic studies at room temperature. Simulations using an iterative projection algorithm show that phasing is feasible with fairly minimal molecular envelope information, supporting recent uniqueness results for this problem Arnal & Millane (2017). Acta Cryst. A73, 438–448. The effects of noise and likely requirements for structure determination using X‐ray free‐electron laser sources are investigated.
Phase retrieval using diffraction data from two‐dimensional crystals and minimal molecular envelope information is examined by simulation. Practical considerations for application to X‐ray free‐electron laser data are discussed.
American Tax Resisters gives a history of the anti-tax movement that, for the past 150 years, has pursued limited taxes on wealth and battled efforts to secure social justice through income ...redistribution. It explains how a once-marginal ideology became mainstream, elevating individual entrepreneurialism over sacrifice and solidarity.
Previous studies have shown that ZBP‐89 (Zfp148) plays a critical role in erythroid lineage development, with its loss at the embryonic stage causing lethal anemia and thrombocytopenia. Its role in ...adult hematopoiesis has not been described. We now show that conditional deletion of ZBP‐89 in adult mouse hematopoietic stem/progenitor cells (HSPC) causes anemia and thrombocytopenia that are transient in the steady state, but readily uncovered following chemically induced erythro/megakaryopoietic stress. Unexpectedly, stress induced by bone marrow transplantation of ZBP89−/− HSPC also resulted in a myeloid‐to‐B lymphoid lineage switch in bone marrow recipients. The erythroid and myeloid/B lymphoid lineage anomalies in ZBP89−/− HSPC are reproduced in vitro in the ZBP‐89‐silenced multipotent hematopoietic cell line FDCP‐Mix A4, and are associated with the upregulation of PU.1 and downregulation of SCL/Tal1 and GATA‐1 in ZBP89‐deficient cells. Chromatin immunoprecipitation and luciferase reporter assays show that ZBP‐89 is a direct repressor of PU.1 and activator of SCL/Tal1 and GATA‐1. These data identify an important role for ZBP‐89 in regulating stress hematopoiesis in adult mouse bone marrow. Stem Cells 2014;32:791–801
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