Rethinking the semantics of attitude reports

In response to John Locke’s death in 1704, Pierre Coste (1824) penned a letter containing the following passage: [H]e was naturally somewhat choleric. But his anger never lasted long...I remember, that two or three weeks before his death, as he was sitting in a garden, taking the air in a bright sunshine, whose warmth afforded him a great deal of pleasure...; we happened to speak of Horace, I know not on what occasion, and having repeated to him these verses, where that Poet says of himself, that he was Solibus aptum; Irasci celerem, tamen ut placabilis essem: “That he loved the warmth of the sun, and that tho’ he was naturally choleric, his anger was easily appeased.” Mr. Locke replied, that if he durst presume to compare himself with Horace in any thing, he thought he was perfectly like him in those two respects. (170, bold emphasis mine) This passage loosely contains a sentence of the form ⌜x says of y that p⌝ and ends with an anaphoric reference to “two respects” that, at face value, are designated by clausal complements, viz. ‘that he loved the warmth of the sun’ and ‘that tho he was naturally choleric, his anger was easily appeased.’ This dissertation concerns the semantics of these and related constructions, with an emphasis placed on those of the form ⌜x believes about y that p.⌝ These belief-about reports have received less attention than reports of the form ⌜x believes that p,⌝ but the former – along with their syntactically derived forms – are just as much a part of present-day, natural language English as the latter. Indeed, once I started studying ‘about’-constructions systematically, I immediately began to notice their regular appearance “in the wild.” This dissertation represents my attempts at taming this small corner, replete with philosophical significance, of the English language. There are three chapters, and they all concern the semantics of attitude verbs with clausal complements; I focus on ‘believes’ for ease of exposition. Chapters 1 and 3 can be read as standalone works. Chapter 2 should be read after Chapter 1. In Chapter 1, “A Puzzle about Belief-about,” I argue that certain valid inferences involving belief-about reports are prima facie inconsistent with orthodox views of the belief relation as binary and propositional. In response, I propose a conservative departure from orthodoxy according to which certain ‘that’-clauses designate novel devices of semantic type called open propositions; the view of belief as binary and propositional is retained. I give some reasons for thinking that open propositions are properties of a certain kind, give a bridge principle between belief-about and belief simpliciter, and formally implement the resulting view in accordance with contemporary theories of syntax and compositional semantics. The upshot is that theorists committed to orthodoxy must complicate their account of certain ‘that’-clauses in surprising ways. In Chapter 2, “Belief is a Ternary Relation,” I object to the semantic complexity required by the proposal advanced in Chapter 1 and investigate a more radical departure from orthodoxy, viz. that belief is a ternary relation between subjects, objects (“targets”), and properties (“contents”). After showing how the resulting Target and Content View can be formally implemented, I respond to a variety of objections that fall roughly into one of two categories: semantic and metaphysical. Responding to the semantic objections requires developing accounts of truth, assertion, and related notions, while responding to the metaphysical objections requires defending a particular view on the nature of propositions. The upshot is that if theorists are unwilling to countenance the semantic complexity required to save orthodoxy in the way proposed in Chapter 1, then the Target and Content View is an attractive alternative with theoretical benefits that are significant in their own right. The formal implementation of the view proposed in Chapter 2 presupposes an intensional semantic framework attributable to the linguistic development of variable-based theories of intensionality, which purport to explain the transparency of determiner phrases in the context of attitude reports. In Chapter 3, “Variable-based Intensionality for Structured Propositions,” I argue that these theories in their simple, traditional forms are not available to advocates of structured propositions, and that the only attempt so far to unify these approaches is unsuccessful. So, I develop an improved variable-based theory of intensionality for structured propositions. Due to the underappreciated generality of the intensional phenomena at issue, however, it turns out that all theories face further challenges still. The upshot is that advocates of structured propositions might even be in a stronger position than other theorists when it comes to tackling these challenges purely semantically, but the complications required also suggest that non-semantic explanations of transparency are worth investigating now more than ever. I’ll end with a note on methodology. This dissertation is couched within the theoretical framework of generative grammar and compositional semantics. One of its guiding principles is, accordingly, that truth-conditions for English sentences in context must be compositionally derived on the basis of syntactically respectable logical forms. This dissertation is also strongly influenced by the methods and tools of contemporary analytic metaphysics. So, another one of its guiding principle is that we ought to take seriously the nature of the entities appealed to by our best scientific theories, including the science of language. A recurring theme is therefore the dovetailing of considerations from formal semantics, on the one hand, and philosophical argumentation pertaining to the metaphysical natures of compositional semantic values (in context), on the other. I’ve tried to treat linguistic and philosophical considerations as on a par with one another throughout, conceiving of their distinction ultimately as an arbitrary matter – or, at least, as one that can be safely bracketed for present purposes.Philosoph

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

A versatile cryo-transfer system, connecting cryogenic focused ion beam sample preparation to atom probe microscopy.

Atom probe tomography (APT) is a powerful technique to obtain 3D chemical and structural information, however the 'standard' atom probe experimental workflow involves transfer of specimens at ambient conditions. The ability to transfer air- or thermally-sensitive samples between instruments while maintaining environmental control is critical to prevent chemical or morphological changes prior to analysis for a variety of interesting sample materials. In this article, we describe a versatile transfer system that enables cryogenic- or room-temperature transfer of specimens in vacuum or atmospheric conditions between sample preparation stations, a focused ion beam system (Zeiss Crossbeam 540) and a widely used commercial atom probe system (CAMECA LEAP 4000X HR). As an example for the use of this transfer system, we present atom probe data of gallium- (Ga)-free grain boundaries in an aluminum (Al) alloy specimen prepared with a Ga-based FIB

Focusing on Mobility

In this paper, we motivate the importance of the field of mobile computing and survey current practical and formal approaches. We argue that the existing formalisms are not sufficiently general and powerful because they do not model all necessary concepts of mobility adequately. The main contribution of the paper is, therefore, to identify and define the fundamental concepts of mobile systems by providing a precise, mathematical foundation. The model we present is an extended variant of existing, compositional network models for control and data flow of non-mobile systems, enriched by the concept of locations as places containing components. To model the migration of a component from one location to another, the containment relation may change dynamically over time. Based on this formal model, we define a numbe

Biosensors supporting healthcare in missions — expert consensus on the status of implementation in the military and future tasks

The monitoring of physiological parameters using wearable (bio-) sensors of military personnel is a progressing process within the military environment. It sets high demands on such devices, in order to support healthcare and performance of the personnel. To get an overview of the current status of the use, the evaluation and the implementation in the military, in May 2021, the Multinational Medical Coordination Centre / European Medical Command has organized an expert workshop about ‘Biosensors Supporting Healthcare in Missions’. Three thematic clusters were addressed: ‘Human Performance and Readiness’; ‘Health and Medical Management Applications’ and ‘Ethical and Legal Aspects of the Use of Biosensors’

Pangenome-based genome inference allows efficient and accurate genotyping across a wide spectrum of variant classes

PanGenie is an alignment-free, k-mer-based tool that utilizes a haplotype-resolved pangenome reference to genotype a wide range of variants. Typical genotyping workflows map reads to a reference genome before identifying genetic variants. Generating such alignments introduces reference biases and comes with substantial computational burden. Furthermore, short-read lengths limit the ability to characterize repetitive genomic regions, which are particularly challenging for fast k-mer-based genotypers. In the present study, we propose a new algorithm, PanGenie, that leverages a haplotype-resolved pangenome reference together with k-mer counts from short-read sequencing data to genotype a wide spectrum of genetic variation-a process we refer to as genome inference. Compared with mapping-based approaches, PanGenie is more than 4 times faster at 30-fold coverage and achieves better genotype concordances for almost all variant types and coverages tested. Improvements are especially pronounced for large insertions (>= 50 bp) and variants in repetitive regions, enabling the inclusion of these classes of variants in genome-wide association studies. PanGenie efficiently leverages the increasing amount of haplotype-resolved assemblies to unravel the functional impact of previously inaccessible variants while being faster compared with alignment-based workflows

Genomic Characterization of Severe Acute Respiratory Syndrome-Related Coronavirus in European Bats and Classification of Coronaviruses Based on Partial RNA-Dependent RNA Polymerase Gene Sequences▿ †

Bats may host emerging viruses, including coronaviruses (CoV). We conducted an evaluation of CoV in rhinolophid and vespertilionid bat species common in Europe. Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high frequencies and concentrations (26% of animals are positive; up to 2.4 × 108 copies per gram of feces), as well as two Alphacoronavirus clades, one novel and one related to the HKU2 clade. All three clades present in Miniopterus bats in China (HKU7, HKU8, and 1A related) were also present in European Miniopterus bats. An additional novel Alphacoronavirus clade (bat CoV [BtCoV]/BNM98-30) was detected in Nyctalus leisleri. A CoV grouping criterion was developed by comparing amino acid identities across an 816-bp fragment of the RNA-dependent RNA polymerases (RdRp) of all accepted mammalian CoV species (RdRp-based grouping units [RGU]). Criteria for defining separate RGU in mammalian CoV were a >4.8% amino acid distance for alphacoronaviruses and a >6.3% distance for betacoronaviruses. All the above-mentioned novel clades represented independent RGU. Strict associations between CoV RGU and host bat genera were confirmed for six independent RGU represented simultaneously in China and Europe. A SARS-related virus (BtCoV/BM48-31/Bulgaria/2008) from a Rhinolophus blasii (Rhi bla) bat was fully sequenced. It is predicted that proteins 3b and 6 were highly divergent from those proteins in all known SARS-related CoV. Open reading frame 8 (ORF8) was surprisingly absent. Surface expression of spike and staining with sera of SARS survivors suggested low antigenic overlap with SARS CoV. However, the receptor binding domain of SARS CoV showed higher similarity with that of BtCoV/BM48-31/Bulgaria/2008 than with that of any Chinese bat-borne CoV. Critical spike domains 472 and 487 were identical and similar, respectively. This study underlines the importance of assessments of the zoonotic potential of widely distributed bat-borne CoV