Tolerance Puzzles

2021 ◽  
pp. 53-78
Author(s):  
Cian Dorr ◽  
John Hawthorne ◽  
Juhani Yli-Vakkuri
Keyword(s):  
Small Difference ◽  
Relevant Parameter ◽  
Modal Variation ◽  
Objective Chance ◽  
General Schema

This chapter provides a general schema for regimenting a broad family of puzzles of modal variation. These puzzles begin with a ‘Tolerance’ premise according to which an objects (or a certain kind of object) can differ in any small way along a certain parameter. This is supplemented with a ‘Non-contingency’ premise according to which the Tolerance premise is necessarily true if true at all, an ‘Iteration’ premise according to which anything possibly possible is possible, and a ‘Persistent Closeness’ premise according to which what counts as a ‘small difference’ is modally constant. These premises jointly imply the conclusion, ‘Hypertolerance’, that the object or objects in question can differ arbitrarily along the relevant parameter. We show how this schema is general enough to subsume puzzles involving time or objective chance, and discuss some difficulties that arise in trying to formulate compelling instantiations of the schema involving variation in originating matter.

Selective Linear Segmentation For Detecting Relevant Parameter Changes

2019 ◽  
Author(s):  
Arnaud Dufays ◽  
Houndetoungan Elysée Aristide ◽  
Alain Coen
Keyword(s):  
Relevant Parameter

The Difference in Sensing Properties Towards Anions between Two Pyridinium Amide-Based Receptors with a Subtle Change of H-Bond Position

2020 ◽  
Vol 17 (6) ◽  
pp. 472-478
Author(s):  
Wei-tao Gong ◽  
Wei-dong Qu ◽  
Guiling Ning
Keyword(s):  
Fluorescence Enhancement ◽  
Small Difference ◽  
Fluorescence Emission ◽  
Subtle Change ◽  
Sensing Properties ◽  
Naked Eye ◽  
Recognition Ability ◽  
The Difference ◽  
L1 And L2

Two pyridinium amide-based receptors L1 and L2 with a small difference of H-bond position of the amide have been synthesized and characterized. Interestingly, they exhibited a huge difference in sensing towards AcO- and H2PO4 -, respectively. Receptor L1 was found to be ‘naked-eye’ selective for AcO- anions, while receptor L2 showed clear fluorescence enhancement selective to H2PO4 - anion. The recognition ability has been established by fluorescence emission, UV-vis spectra, and 1HNMR titration.

Acting on Knowledge

2017 ◽  
Author(s):  
Timothy Williamson
Keyword(s):  
Practical Reasoning ◽  
Philosophy Of Action ◽  
Plausible Account ◽  
Direction Of Fit ◽  
General Schema ◽  
Action Intention ◽  
Knowledge Norms

This chapter develops and refines the analogy between knowledge and action in Knowledge and its Limits. The general schema is: knowledge is to belief as action is to intention. The analogy reverses direction of fit between mind and world. The knowledge/belief side corresponds to the inputs to practical reasoning, the action/intention side to its outputs. Since desires are inputs to practical reasoning, the desire-as-belief thesis is considered sympathetically. When all goes well with practical reasoning, one acts on what one knows. Belief plays the same local role as knowledge, and intention as action, in practical reasoning. This is the appropriate setting to understand knowledge norms for belief and practical reasoning. Marginalizing knowledge in epistemology is as perverse as marginalizing action in the philosophy of action. Opponents of knowledge-first epistemology are challenged to produce an equally systematic and plausible account of the relation between the cognitive and the practical.

scholarly journals Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Benincasa ◽  
C Schiano ◽  
T Infante ◽  
M Franzese ◽  
R Casale ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cpg Island ◽  
Methylation Profile ◽  
Integrated Analysis ◽  
Funding Source ◽  
Relevant Parameter ◽  
Cardiac Computed Tomography Angiography ◽  
Dna Methylation Profile

Abstract Aims Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups. Conclusions Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health

scholarly journals Carbon Isotope Fractionation during the Formation of CO2 Hydrate and Equilibrium Pressures of 12CO2 and 13CO2 Hydrates

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4215
Author(s):  
Hiromi Kimura ◽  
Go Fuseya ◽  
Satoshi Takeya ◽  
Akihiro Hachikubo
Keyword(s):  
Carbon Isotope ◽  
Isotope Fractionation ◽  
Small Difference ◽  
Hydrate Formation ◽  
Formation Temperature ◽  
Carbon Isotope Fractionation ◽  
Unit Cell Size ◽  
Naturally Occurring ◽  
Three Phase ◽  
The Difference

Knowledge of carbon isotope fractionation is needed in order to discuss the formation and dissociation of naturally occurring CO2 hydrates. We investigated carbon isotope fractionation during CO2 hydrate formation and measured the three-phase equilibria of 12CO2–H2O and 13CO2–H2O systems. From a crystal structure viewpoint, the difference in the Raman spectra of hydrate-bound 12CO2 and 13CO2 was revealed, although their unit cell size was similar. The δ13C of hydrate-bound CO2 was lower than that of the residual CO2 (1.0–1.5‰) in a formation temperature ranging between 226 K and 278 K. The results show that the small difference between equilibrium pressures of ~0.01 MPa in 12CO2 and 13CO2 hydrates causes carbon isotope fractionation of ~1‰. However, the difference between equilibrium pressures in the 12CO2–H2O and 13CO2–H2O systems was smaller than the standard uncertainties of measurement; more accurate pressure measurement is required for quantitative discussion.

scholarly journals Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia

2021 ◽  
Vol 22 (2) ◽  
pp. 660
Author(s):  
María Aguilar-Ballester ◽  
Gema Hurtado-Genovés ◽  
Alida Taberner-Cortés ◽  
Andrea Herrero-Cervera ◽  
Sergio Martínez-Hervás ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Leukocyte Adhesion ◽  
Experimental Studies ◽  
Lipid Lowering ◽  
Foam Cell Formation ◽  
Relevant Parameter

Cardiovascular disease (CVD) is the leading cause of death worldwide and is the clinical manifestation of the atherosclerosis. Elevated LDL-cholesterol levels are the first line of therapy but the increasing prevalence in type 2 diabetes mellitus (T2DM) has positioned the cardiometabolic risk as the most relevant parameter for treatment. Therefore, the control of this risk, characterized by dyslipidemia, hypertension, obesity, and insulin resistance, has become a major goal in many experimental and clinical studies in the context of CVD. In the present review, we summarized experimental studies and clinical trials of recent anti-diabetic and lipid-lowering therapies targeted to reduce CVD. Specifically, incretin-based therapies, sodium-glucose co-transporter 2 inhibitors, and proprotein convertase subtilisin kexin 9 inactivating therapies are described. Moreover, the novel molecular mechanisms explaining the CVD protection of the drugs reviewed here indicate major effects on vascular cells, inflammatory cells, and cardiomyocytes, beyond their expected anti-diabetic and lipid-lowering control. The revealed key mechanism is a prevention of acute cardiovascular events by restraining atherosclerosis at early stages, with decreased leukocyte adhesion, recruitment, and foam cell formation, and increased plaque stability and diminished necrotic core in advanced plaques. These emergent cardiometabolic therapies have a promising future to reduce CVD burden.

scholarly journals Hybrid Cyclobutane/Proline-Containing Peptidomimetics: The Conformational Constraint Influences Their Cell-Penetration Ability

2021 ◽  
Vol 22 (10) ◽  
pp. 5092
Author(s):  
Ona Illa ◽  
Jimena Ospina ◽  
José-Emilio Sánchez-Aparicio ◽  
Ximena Pulido ◽  
María Ángeles Abengozar ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Penetrating Peptides ◽  
Cell Uptake ◽  
Relevant Parameter ◽  
Intracellular Accumulation ◽  
Peptide Backbone ◽  
New Family ◽  
Cell Line Hela ◽  
Penetration Ability ◽  
Tumoral Cell

A new family of hybrid β,γ-peptidomimetics consisting of a repetitive unit formed by a chiral cyclobutane-containing trans-β-amino acid plus a Nα-functionalized trans-γ-amino-l-proline joined in alternation were synthesized and evaluated as cell penetrating peptides (CPP). They lack toxicity on the human tumoral cell line HeLa, with an almost negligible cell uptake. The dodecapeptide showed a substantial microbicidal activity on Leishmania parasites at 50 µM but with a modest intracellular accumulation. Their previously published γ,γ-homologues, with a cyclobutane γ-amino acid, showed a well-defined secondary structure with an average inter-guanidinium distance of 8–10 Å, a higher leishmanicidal activity as well as a significant intracellular accumulation. The presence of a very rigid cyclobutane β-amino acid in the peptide backbone precludes the acquisition of a defined conformation suitable for their cell uptake ability. Our results unveiled the preorganized charge-display as a relevant parameter, additional to the separation among the charged groups as previously described. The data herein reinforce the relevance of these descriptors in the design of CPPs with improved properties.

Cubical Agda: A dependently typed programming language with univalence and higher inductive types

2021 ◽  
Vol 31 ◽  
Author(s):  
ANDREA VEZZOSI ◽  
ANDERS MÖRTBERG ◽  
ANDREAS ABEL
Keyword(s):  
Programming Language ◽  
Type Theory ◽  
Type Checking ◽  
Dependent Type Theory ◽  
Wide Range ◽  
General Schema ◽  
Direct Definition ◽  
Inductive Types ◽  
Definition Of ◽  
Cubical Type Theory

Abstract Proof assistants based on dependent type theory provide expressive languages for both programming and proving within the same system. However, all of the major implementations lack powerful extensionality principles for reasoning about equality, such as function and propositional extensionality. These principles are typically added axiomatically which disrupts the constructive properties of these systems. Cubical type theory provides a solution by giving computational meaning to Homotopy Type Theory and Univalent Foundations, in particular to the univalence axiom and higher inductive types (HITs). This paper describes an extension of the dependently typed functional programming language Agda with cubical primitives, making it into a full-blown proof assistant with native support for univalence and a general schema of HITs. These new primitives allow the direct definition of function and propositional extensionality as well as quotient types, all with computational content. Additionally, thanks also to copatterns, bisimilarity is equivalent to equality for coinductive types. The adoption of cubical type theory extends Agda with support for a wide range of extensionality principles, without sacrificing type checking and constructivity.

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