Enumeration of Quadrangular Dissections of the Disk

1965 ◽  
Vol 17 ◽  
pp. 302-317 ◽  
Author(s):  
William G. Brown
Keyword(s):  
Cell Complex ◽  
List Type ◽  
Closed Disk ◽  
A Cell

A dissection of the disk will be a cell complex (1, p. 39) K with polyhedron the closed disk B2. It will further be required that: (a) every edge of K be incident with two distinct vertices (called its ends) ;(b) no two edges have the same ends ; and(b) no two edges have the same ends ; and

scholarly journals Differential aberrant structural synaptic plasticity in axons and dendrites ahead of their degeneration in tauopathy

2020 ◽  
Author(s):  
Johanna S. Jackson ◽  
James D. Johnson ◽  
Soraya Meftah ◽  
Tracey K Murray ◽  
Zeshan Ahmed ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Disease Progression ◽  
Dendritic Spines ◽  
Time Course ◽  
Neuronal Degeneration ◽  
List Type ◽  
Synapse Plasticity ◽  
Synapse Density ◽  
A Cell ◽  
Neurite Degeneration

AbstractNeurodegeneration driven by aberrant tau is a key feature of many dementias. Pathological stages of tauopathy are characterised by reduced synapse density and altered synapse function. Furthermore, changes in synaptic plasticity have been documented in the early stages of tauopathy suggesting that they may be a driver of later pathology. However, it remains unclear if synapse plasticity is specifically linked to the degeneration of neurons. This is partly because, in progressive dementias, pathology can vary widely from cell-to-cell along the prolonged disease time-course. To overcome this variability, we have taken a longitudinal experimental approach to track individual neurons through the progression of neurodegenerative tauopathy. Using repeated in vivo 2-photon imaging in rTg4510 transgenic mice, we have measured structural plasticity of presynaptic terminaux boutons and postsynaptic spines on individual axons and dendrites over long periods of time. By following individual neurons, we have measured synapse density across the neuronal population and tracked changes in synapse turnover in each neuron. We found that tauopathy drives a reduction in density of both presynaptic and postsynaptic structures and that this is partially driven by degeneration of individual axons and dendrites that are spread widely across the disease time-course. Both synaptic loss and neuronal degeneration was ameliorated by reduction in expression of the aberrant P301L transgene, but only if that reduction was initiated early in disease progression. Notably, neurite degeneration was preceded by alterations in synapse turnover that contrasted in axons and dendrites. In dendrites destined to die, there was a dramatic loss of spines in the week immediately before degeneration. In contrast, axonal degeneration was preceded by a progressive attenuation of presynaptic turnover that started many weeks before axon disappearance. Therefore, changes in synapse plasticity are harbingers of degeneration of individual neurites that occur at differing stages of tau-driven neurodegenerative disease, suggesting a cell or neurite autonomous process. Furthermore, the links between synapse plasticity and degeneration are distinct in axonal and dendritic compartments.Key findingsTauopathy driven by tau P301L in rTg4510 mice causes a progressive decrease in density of presynaptic terminaux boutons and postsynaptic dendritic spines in cortical excitatory neurons.Longitudinal imaging of individual axons and dendrites shows that there is a huge diversity of effects at varying times in different cells.Decreases in overall synapse density are driven partly, but not exclusively, by degeneration of dendrites and axons that are distributed widely across the time-course of disease.Suppression of pathological P301L tau expression can ameliorate accumulation of tau pathology, synapse loss and neurodegeneration, but only if administered early in disease progression.Neurite degeneration is preceded by aberrant structural synaptic plasticity in a cell-specific way that is markedly different in dendrites and axons.Degeneration of dendrites is immediately preceded by dramatic loss of dendritic spines.Axonal loss is characterised by a progressive attenuation of presynaptic bouton plasticity that starts months before degeneration.

scholarly journals Evaluating Cell Identity from Transcription Profiles

2018 ◽  
Author(s):  
Nancy Mah ◽  
Katerina Taškova ◽  
Khadija El Amrani ◽  
Krithika Hariharan ◽  
Andreas Kurtz ◽  
...  
Keyword(s):  
Target Cell ◽  
Drug Testing ◽  
Cell Types ◽  
Patient Specific ◽  
List Type ◽  
Cell Type ◽  
Cell Identity ◽  
Transcription Profiles ◽  
Cell Based Therapy ◽  
A Cell

SummaryInduced pluripotent stem cells (iPS) and direct lineage programming offer promising autologous and patient-specific sources of cells for personalized drug-testing and cell-based therapy. Before these engineered cells can be widely used, it is important to evaluate how well the engineered cell types resemble their intended target cell types. We have developed a method to generate CellScore, a cell identity score that can be used to evaluate the success of an engineered cell type in relation to both its initial and desired target cell type, which are used as references. Of 20 cell transitions tested, the most successful transitions were the iPS cells (CellScore > 0.9), while other transitions (e.g. induced hepatocytes or motor neurons) indicated incomplete transitions (CellScore < 0.5). In principle, the method can be applied to any engineered cell undergoing a cell transition, where transcription profiles are available for the reference cell types and the engineered cell type.HighlightsA curated standard dataset of transcription profiles from normal cell types was created.CellScore evaluates the cell identity of engineered cell types, using the curated dataset.CellScore considers the initial and desired target cell type.CellScore identifies the most successfully engineered clones for further functional testing.

scholarly journals A cell complex in number theory

2011 ◽  
Vol 46 (1-4) ◽  
pp. 71-85 ◽  
Author(s):  
Anders Björner
Keyword(s):  
Number Theory ◽  
Cell Complex ◽  
A Cell

scholarly journals Some small aspherical spaces

1973 ◽  
Vol 16 (3) ◽  
pp. 332-352 ◽  
Author(s):  
Eldon Dyer ◽  
A. T. Vasquez
Keyword(s):  
Euclidean Space ◽  
Fundamental Group ◽  
Homotopy Type ◽  
Homotopy Group ◽  
Continuous Mapping ◽  
Cell Complex ◽  
A Cell

Let Sn denote the sphere of all points in Euclidean space Rn + 1 at a distance of 1 from the origin and Dn + 1 the ball of all points in Rn + 1 at a distance not exceeding 1 from the origin The space X is said to be aspherical if for every n ≧ 2 and every continuous mapping: f: Sn → X, there exists a continuous mapping g: Dn + 1 → X with restriction to the subspace Sn equal to f. Thus, the only homotopy group of X which might be non-zero is the fundamental group τ1(X, *) ≅ G. If X is also a cell-complex, it is called a K(G, 1). If X and Y are K(G, l)'s, then they have the same homotopy type, and consequently

scholarly journals UNIFORM APPROXIMATION BY POLYNOMIAL, RATIONAL AND ANALYTIC FUNCTIONS

2008 ◽  
Vol 77 (3) ◽  
pp. 387-399
Author(s):  
T. G. HONARY ◽  
S. MORADI
Keyword(s):  
Rational Functions ◽  
Function Algebra ◽  
Continuous Functions ◽  
Compact Set ◽  
List Type ◽  
Type Number ◽  
Open Disk ◽  
Closed Disk ◽  
Open Set ◽  
Image Position

AbstractLet K and X be compact plane sets such that $K\subseteq X$. Let P(K) be the uniform closure of polynomials on K, let R(K) be the uniform closure of rational functions on K with no poles in K and let A(K) be the space of continuous functions on K which are analytic on int(K). Define P(X,K),R(X,K) and A(X,K) to be the set of functions in C(X) whose restriction to K belongs to P(K),R(K) and A(K), respectively. Let S0(A) denote the set of peak points for the Banach function algebra A on X. Let S and T be compact subsets of X. We extend the Hartogs–Rosenthal theorem by showing that if the symmetric difference SΔT has planar measure zero, then R(X,S)=R(X,T) . Then we show that the following properties are equivalent: (i)R(X,S)=R(X,T) ;(ii)$S\setminus T\subseteq S_0(R(X,S))$ and $T\setminus S\subseteq S_0(R(X,T))$;(iii)R(K)=C(K) for every compact set $K \subseteq S\Delta T$;(iv)$R(X,S \cap \overline {U})=R(X,T \cap \overline {U})$ for every open set U in ℂ ;(v)for every p∈X there exists an open disk Dp with centre p such that We prove an extension of Vitushkin’s theorem by showing that the following properties are equivalent: (i)A(X,S)=R(X,T) ;(ii)$A(X,S \cap \overline {D})=R(X,T \cap \overline {D})$ for every closed disk $\overline {D}$ in ℂ ;(iii)for every p∈X there exists an open disk Dp with centre p such that

722 Inhibition of integrin avß8-Mediated TGF-ß activation with C6D4 provides improved potency and selectivity vs general TGF-ß inhibitors for cancer immunotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A764-A765
Author(s):  
Robert Seed ◽  
Stephen Nishimura
Keyword(s):  
T Cells ◽  
Cell Surface ◽  
Immune Evasion ◽  
Inhibitory Activity ◽  
Cell Surface Expression ◽  
List Type ◽  
Reporter System ◽  
Wide Range ◽  
Activation System ◽  
A Cell

BackgroundTGF-ß plays a key role in immune evasion as a critical regulator of both innate and adaptive tumor immunity and promotes broad immunosuppressive effects on numerous inflammatory cell subpopulations ultimately resulting in tumor immune tolerance and evasion.1 It has also been implicated in resistance to immune checkpoint therapies, and additive or synergistic effects of dual TGF-ß and PD-1 inhibition has been reported.2 3 A number of TGF-ß inhibitors are in clinical development with different modes of action. Most protein-based inhibitors are designed to block diffusible TGF-ß from interacting with its proximal signaling receptor TGF-ßR2 and includes monoclonal antibodies (Mabs) and receptor traps. This investigation compares inhibition of TGF-ß by a number of inhibitors and the integrin avß8 (C6D4) to assess their relative potential as cancer therapeutics.MethodsNo reporter system currently exists to investigate the mechanistic basis of cell-intrinsic TGF-ß activation, whereby the L-TGF-ß presenting cell is also the cell that responds toTGF-ß signaling (figure 1). To build a cell-intrinsic TGF-ß activation system, TMLC cells were stably transfected with wild-type (WT) TGF-ß. Without co-transfecting GARP, TMLC do not present L-TGF-ß on their cell surface. When co-transfected with TGF-ß and GARP, high levels of cell surface expression of L-TGF-ß are detected. Additionally, to build a cell-intrinsic TGF-ß activation system which express a non-releasable form of TGF-ß, we mutated the L-TGF-ß furin cleavage site (R249A) and similarly expressed the L-TGF-ß(R249A)/GARP complex on the surface of TGF-ß reporter cells (TMLC). These cell-intrinsic TGF-ß activation systems were used to assess the relative abilities of Mabs avß8, TGF-ß, TGF-ßR2, GARP or TGF-ßR2 receptor trap to inhibit avß8-mediated TGF-ß activation.Results avß8 exhibited superior inhibitory activity compared with other TGF-ß inhibitors, which was similar in both diffusible and non-diffusible models (figure 2). The biologic relevance of these finding was confirmed using CD4+ T-cells in place of the reporter cells where TGF-ß-dependent Treg generation was almost completely blocked by avß8 but was poorly inhibited by the other TGF-ß inhibitors.Abstract 722 Figure 1Novel cell-intrinsic TGF-β reporter systemAbstract 722 Figure 2Inhibition curves showing inhibition of αvβ8-mediated TGF-β activation by various inhibitors including anti-β8 (C6D4) in a model of diffusible (A) or non-diffusible ((R249A mutant) L-TGF-β (B)ConclusionsIn this study avß8 exhibited dramatic TGF-ß inhibitory activity compared with a wide range of inhibitors in development. Because integrin avß8 may direct TGF-ß signaling from within its latent complex, this may offer an advantage for target specificity and avoid the challenges faced by non-specific TGF-ß inhibitors. These findings characterize avß8 as a novel and potent immunotherapy drug for further clinical investigation.Trial RegistrationNAEthics ApprovalNAReferencesBatlle E, Massagué J. Transforming growth factor-ß signaling in immunity and cancer. Immunity. 2019;50(4):924–940.Tauriello DVF, Palomo-Ponce S, Stork D, et al. TGFß drives immune evasion in genetically reconstituted colon cancer metastasis. Nature 2018;554(7693):538–543.Mariathasan S, Turley SJ, Nickles D, et al. TGFß attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 2018;554(7693):544–548.

scholarly journals 125 Reexamination of MAGE-A3 as a T-cell Therapeutic Target

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A136-A136
Author(s):  
Aaron Martin ◽  
Xueyin Wang ◽  
Han Xu ◽  
Alexander Kamb ◽  
Mark Sandberg ◽  
...  
Keyword(s):  
High Selectivity ◽  
Significant Risk ◽  
Genomic Research ◽  
List Type ◽  
Recurrent Cancer ◽  
The Past ◽  
A Cell ◽  
Hybridization In Situ ◽  
The Brain

BackgroundRecurrent cancer-specific targets are rare. Given the pace of genomic research over the past three decades, few are likely to lie yet undiscovered. In 2013 an innovative MAGE-A3-directed cancer therapeutic of great potential value was terminated in the clinic because of neurotoxicity.1 The safety problems were hypothesized to originate from off-target TCR activity against a closely related MAGE-A12 peptide.MethodsA combination of published and new data led us to test this hypothesis with current technology, including RNA hybridization in situ and further analysis of the clinical TCR’s specificity to MAGE-A12 and other antigens.ResultsWe find that a key prediction of the MAGE-A12 toxicity hypothesis, the existence of rare, high-MAGE-A12-expressing cells in the brain, is not supported by the data. Our results imply that an alternative related peptide from the EPS8L2 protein is more likely responsible for the toxicity. Therefore, it may be valuable to reconsider MAGE-A3 as a cancer target using HLA-A*02-restricted-TCRs or CARs. As a step in this direction, we isolated MAGE-A3 pMHC-directed CARs, targeting the same peptide as the clinical TCR. These CARs have high selectivity, and avoid cross-reaction with the EPS8L2 peptide that represents a significant risk for MAGE-A3-targeted therapeutics.ConclusionsGiven the qualities of MAGE-A3 as an onco-testis antigen widely expressed in tumors and largely absent from normal adult tissues, our findings suggest that MAGE-A3 may deserve further consideration as a cancer target. We have identified CARs with selectivity profiles consistent with a cell therapeutic directed against HLA-A*02-positive, MAGE-A3-expressing cancers. The relative merits of TCRs and CARs for this target will be discussed.ReferenceMorgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, et al. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 2013;36:133–151, doi:10.1097/CJI.0b013e3182829903.

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