bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of Retroviral Vectors in Clinical Applications: Lessons from Retroviral Biology and Pathogenesis
Authors: Neil James C 
Published: November 2017

Abstract

The ability of retroviruses to integrate a precise copy of the viral genome into host cell DNA (deoxyribonucleic acid) has been harnessed in the development of retroviral vectors for stable delivery of foreign genes to target cells. Over several decades, these tools have been utilised in human medicine in diverse applications from cell lineage tracing by gene marking to correction of single‐gene disorders and therapy of cancer. The unanticipated occurrence of leukaemias due to vector insertional mutagenesis in trials of gene therapy led to an urgent search for safer vectors and delivery systems. The advent of T‐cell therapy for cancer has led to renewed interest in retroviral vectors as stable and efficient delivery vehicles and is supported by observations suggesting that mature T cells are relatively resistant to oncogenic transformation by retroviruses. However, this evidence is circumstantial and the long‐term risks are poorly understood. Retroviral vector safety is considered here from the perspective of the biology and pathogenesis of their parental viruses. It is suggested that robust cell suicide strategies to remove transduced cells are likely to be important if retroviral vectors are to be adopted widely for delivery of T‐cell therapy for cancer and other diseases.

Key Concepts

Retroviral vectors are useful tools for delivery of foreign genes to host cells
in vitro
and
in vivo
.

The term retroviral vector is generally used for a vector based on a gamma‐retrovirus such as murine leukaemia virus.

The term lentiviral vector is generally used for a vector based on human immunodeficiency virus type 1.

Retroviral vectors have been tested in many clinical applications including cell lineage tracing, gene therapy and cancer therapy.

Retroviruses can cause disease due to insertional mutagenesis or transduction of host cell genes.

Retroviral and lentiviral integration are nonrandom processes that favour active regions of the genome, increasing the risks of insertional mutagenesis.

Examples of retroviral transduction of host genes include a T‐cell receptor β‐chain gene, providing a parallel with cells engineered for use in T‐cell therapy of cancer.
CRISPR‐Cas9
: A New Tool for Gene Therapy
Authors: Sharma Saumya , Maiti Souvik , Chakraborty Debojyoti 
Published: November 2017

Abstract

Programmable RNA (ribonucleic acid)‐guided genome engineering using the recently developed clustered regularly interspaced short palindromic repeats (CRISPR)‐associated (CRISPR Cas) system has revolutionised the field of gene editing owing its adaptability and versatility in addressing a wide range of biological questions. It relies on harnessing critical components of the bacterial acquired immune system, namely the Cas9 protein and its associated guide ribonucleic acid (gRNA), to selectively target and edit a desired gene, thereby underscoring its potential as a promising gene therapy agent. Its application, however, encompasses several critical parameters, ranging from safe delivery of the agent to tackling issues of unintended off‐targeting in the genome. Similar to its predecessor molecular scissors, namely zinc finger nucleases (ZFNs) and transcription activator‐like nucleases (TALENs), CRISPR‐Cas9 has been studied extensively along these lines to facilitate its use in therapeutic interventions and has shown some early promise in taking benchtop discoveries to the clinic.

Key Concepts

CRISPR‐Cas9 is the most recent addition to the repertoire of ‘molecular scissors’ for genome editing.

The system relies on an RNA‐guided protein that can make desirable changes in the genome.

CRISPR‐Cas9 has shown a lot of promise for
in vivo
and
in vitro
editing, which can be translatable for disorders, particularly monogenic ones.

Components of the system have been used for correcting several disease‐relevant mutations in mice through zygotic, somatic or
ex vivo
gene‐editing strategies.

The success of CRISPR as a therapeutic tool depends on its inherent properties of efficiency and specificity.

Protein and sgRNA engineering combined with improved delivery strategies have led to the discovery of potent CRISPR‐based therapy products.

The first clinical trials using CRISPR are currently under process.
External Possession and Possessor Raising
Authors: Deal Amy Rose 
Published: November 2017

Abstract
External possession is a phenomenon where a nominal is syntactically encoded as a verbal dependent but semantically understood as the possessor of one of its co‐arguments. While the general pattern is cross‐linguistically very common, there is much variation in its precise syntax and semantics. In this chapter, I review the classic analyses of external possession as possessor raising and possessor binding. The evidence behind these analyses indicates that raising and binding are indeed each appropriate for certain subtypes of external possession, as is an analysis in terms of movement to thematic positions. I propose a typology that groups these analyses under the first of two major types of external possession. This first type presents significant parallels to the domain of raising and control, subsuming possessor raising, possessor binding, possessor control, and a variant of exceptional case marking (ECM). Examples are found in Nez Perce, German, Brazilian Portuguese, and English. A second major type of external possession involves subjects only and brings information structural effects. Examples are found in Malagasy, Chickasaw, Tz'utujil, and Japanese.
Ellipsis in Noun Phrases
Authors: Lobeck Anne , Sleeman Petra 
Published: November 2017

AbstractIn early analyses of nominal ellipsis in generative syntax, ellipsis was analyzed as null anaphora, where missing material is interpreted under identity with an antecedent in much the same way as a lexical pronoun. Ellipsis was analyzed either as the result of a deletion transformation, in which ellipsis results from deletion of a lexical pro‐form,one, or as a base‐generated empty category subject to rules of interpretation. Within the Principles and Parameters framework, nominal ellipsis was subsequently analyzed as involving proper government ofpro, an empty pronominal category, which has to be licensed and identified. This approach led to in‐depth, cross‐linguistic analyses of the properties of the determiner and quantifier systems to determine the feature specifications of different functional heads, and the role those features play in licensing and identification. This research also explored connections between ellipsis in DP and substantive adjective and partitive constructions, in particular partitives which involve cliticen(French) andne(Italian). In current research the same questions are still debated, but in more recent theoretical frameworks: the Minimalist Program, Distributed Morphology and Cartography. The questions concern PF‐deletion or late insertion, the role of functional projections such as Classifier Phrase and nP, and the role of focus.
Double Nominatives in Japanese
Authors: Tateishi Koichi 
Published: November 2017

Abstract

It is well known that nominative subjects can be doubled or multiplied in Japanese in ordinary clausal contexts. Various types of analysis have been proposed on the topic. However, many of them mix up notions involved in the issue of the Double Nominative Construction in Japanese. First of all, it has never been logically proven that it is nominative that is involved in the construction (and in “subjecthood” in Japanese in general). Second, nominatives, doubled or not, have “semantic” contents that English nominative subjects do not have. Third, if, in the Government‐and‐Binding/‐Minimalist spirit, the nominative is assigned/licensed by a functional category in Japanese, then we will be situated in a paradoxical state in which case (including nominative) can be multiplied but complementizers can not necessarily. Fourth, in Japanese, the mode of realization of case is different from that in languages like English, as a result of which various sorts of case particles are developed therein. Finally, we do not yet know the true relationship between Japanese case particles and Japanese “adverbial” particles such as
wa
(
top
) and
mo
‘also’. The conventional term “matrix clause phenomena” cannot explain everything on this. In a nutshell, to discuss and analyze the Double Nominative Construction in Japanese, we need to know what the subject is in Japanese, what case is, and whether case in some sense exists in Japanese at all. Various types of Double Nominative/Subject Constructions are compared and it will be pointed out that we at least need to keep in mind several levels of “subjecthood” when we come to discussions of Japanese subjects/nominatives.
Freezing Effects
Authors: Corver Norbert 
Published: November 2017

AbstractThe notion of freezing refers to the phenomenon whereby a constituent becomes an island for extraction when that constituent has undergone syntactic movement (displacement). In other words, the constituent is opaque (“frozen”) in its movement‐derived position. This chapter presents different types of movement‐derived syntactic configurations that display freezing effects and discusses various approaches that have been proposed in generative grammar in order to account for the frozen status of displaced constituents. The chapter further addresses the question as to whether a displaced constituent is an absolute barrier for extraction. That is, are there syntactic configurations from which extraction out of a displaced constituent is possible after all?
Verb‐Initial Word Orders, Primarily in Austronesian and Mayan Languages
Authors: Clemens Lauren Eby , Polinsky Maria 
Published: November 2017

AbstractThis chapter presents several approaches to the syntax of verb‐initial (V1) languages with a special emphasis on Mayan and Austronesian languages. Some V1 languages are strictly VSO, others are VOS, and a significant number combine both orders. This chapter focuses on data from VSO/VOS languages and the factors that underlie these alternations. A number of V1 languages can be more adequately characterized as predicate‐initial, with V1 representing just a subset of possible clause‐initial predicates. The chapter presents a number of structural properties that are or may be associated with V1 and discusses possible implicational relations between such properties and V1. While there are certain common characteristics observed across V1 languages, it is also clear that there are several distinct subtypes of V1. These subtypes call for different syntactic analyses; main approaches include the derivation of V1 via phrasal movement (VP‐raising) and via head‐movement (verb‐raising). Other syntactic approaches to the derivation of V1 include the parametrization of specifier direction within a single language, non‐configurational syntax, and subject lowering. In addition to these purely syntactic analyses, several recent approaches place the derivation of V1 outside syntax or at the syntax–PF interface. Careful, in‐depth analyses of individual languages are required to test the different approaches to V1; in quite a few cases such analyses are still lacking.
Control Phenomena
Authors: Potsdam Eric , Haddad Youssef A. 
Published: November 2017

AbstractControl phenomena have been at the center of syntactic theorizing almost since the inception of generative grammar. To first approximation, control is an interpretive dependency between two arguments: a lexicalized noun phrase (the controller) and a null argument in a dependent clause (the controllee), as inSandyhopes [∅to succeed]. The primary concerns of syntactic theories have been accounting for various characteristics of the null controllee and the identification of its controller. This chapter surveys some of the phenomena that have driven our current understanding of these issues. Within the domain of obligatory control, some phenomena speak to the controller: the behavior of polyadic predicates, implicit control, variable control and control shift, and exceptional cases likepromise. Other phenomena speak to the controllee: exhaustive control, partial control, split control, and control in embedded questions. Assuming that non‐obligatory control is a kind of elsewhere case, the phenomena relevant to non‐obligatory control are those where obligatory control restrictions on controller choice fail to materialize: control into subjects, extraposed clauses, and some adjunct clauses. The chapter also discusses phenomena with a non‐canonical realization of the control relation: backward control and copy control. Within the context of these phenomena, the chapter surveys current generative approaches to the analysis of control: dominant PRO‐based approaches, the movement theory of control, and restructuring analyses. Relative strengths and weaknesses are highlighted.
Measure Phrases and Semi‐Lexical Nouns
Authors: Csirmaz Anikó , Stavrou Melita 
Published: November 2017

AbstractMeasure phrases (MPs, e.g., “two pounds”) appear in a wide variety of environments: nominal, adjectival, adpositional, and verbal structures. The goal of the chapter is to present an overview of the variety of constructions involving MPs as well as the different treatments that were proposed for these structures. Accordingly, the chapter reviews the internal structure of measure expressions as well as the function (predicate nominal, modifier or argument) and position of MPs inside the larger structures that contain them. The structures to be discussed include positive and differential MPs, which appear with adjectives as well as in compound, partitive, and pseudopartitive constructions with nominals. The chapter also addresses variation in the acceptability of MPs, both language‐internally and across languages, as well as the cross‐linguistically distinct realizations of structures that contain MPs. Other topics to be discussed are issues specific to spatial (“twenty miles”) and temporal measure expressions (“twenty minutes”) as well as classifier and container constructions.
Article Doubling
Authors: Lekakou Marika 
Published: November 2017

AbstractThis chapter deals with the doubling of the definite and indefinite article. After a brief introduction to the syntactic and semantic function of (in)definite articles and to the relevance of doubling for syntactic and semantic research, I review the main instantiations of each type of phenomenon. I deal with definite doubling as it is attested in North Germanic languages, in Modern Greek, and in Hebrew. Doubling occurs in these varieties predominantly when adjectival modification is involved; it is obligatory in Hebrew and in certain Northern Germanic languages, and optional in Greek, where it incurs semantic effects related to the restrictive interpretation of the adjective. In the case of Hebrew and Northern Germanic, the debate has revolved around the choice between head movement and phrasal movement within a determiner phrase (DP) analysis of nominals and around the status of the doubling elements; for Hebrew, the idea of a concord relation between the doubling elements has also been exploited. In the case of Greek, major points of controversy have been whether doubling involves an underlying predicative structure and a DP‐internal focus projection. Indefinite doubling is much less widespread cross‐linguistically. It is known to occur in some dialectal variants of Swedish and Norwegian, where it can be argued to involve a predication structure. A different instance of indefinite doubling occurs in Bavarian in the presence of quantificational elements. In this final case, doubling is argued to involve non‐identical elements. The suggestion is made that indefinite doubling as such does not exist at all.
Prolepsis
Authors: Salzmann Martin 
Published: November 2017

AbstractThe linguistic termprolepsisrefers to a construction where a structural complement of the matrix verb is semantically related to the predicate of an embedded clause. In an example likeI believe of John that he likes Mary, the proleptic constituentJohnis related to the position occupied by the coreferential pronounhe.. At first sight one may take the proleptic constituent to be an argument of the matrix verb with the pronoun establishing an anaphoric dependency, but things are more complex. First, the construction is possible with a very wide range of matrix verbs, casting doubt on the argumenthood of the object. Second, a coreferential element is obligatory, which argues against a mere aboutness relationship. There is conflicting evidence concerning the base position of the proleptic object. On the one hand, there is solid evidence from anaphor binding and superiority that the proleptic object occupies an A‐position in the matrix clause. On the other hand, the proleptic object reconstructs into the complement clause. This suggests that the proleptic object originates in the embedded clause, but an analysis involving movement from the complement clause fails for conceptual (Improper Movement, Freezing) and empirical (selective reconstruction effects) reasons. It is proposed that these paradoxical properties follow if the proleptic object is licensed by predication. The complement clause involves a base‐generated operator which turns it into an open sentence. The coreferential pronoun is the variable bound by the operator. The proleptic object, then, is the subject of the predication. The relationship between the proleptic object and the silent operator involves ellipsis, as does the relationship between the operator and the coreferential pronoun. Ellipsis derives the (selective) reconstruction effects, and predication explains the necessity of a coreferential element.
Pied‐Piping
Authors: Horvath Julia 
Published: November 2017

ABSTRACT“Pied‐piping” has been viewed throughout the evolution of generative grammar as involving the displacement of a constituent that is larger than, and properly contains, the element the particular movement operation is normally targeting (such as awh‐word contained within some larger phrase, e.g.,which (boy)/whoseinwhich boy's father/whose friends). Being an effect directly associated with movement operations, its status and accounts have undergone significant shifts in the course of the evolution of the theory of grammar. The chapter provides a comprehensive overview of pied‐piping phenomena and discusses proposed analyses along with the theoretical contexts in which they arose. It lays out the variety of pied‐piping effects and central generalizations observed in the literature of the past decades regarding what pretheoretically can be considered pied‐piping structures. Starting with Ross' Pied‐Piping Convention, the chapter critically assesses the status and treatments of (apparent) pied‐piping, from Ross’ stipulation of a split between what triggers movement and what size constituents end up moving, via the Government and Binding model's “feature percolation” mechanisms and “Move α,” to potential accommodation of pied‐piping effects within the Minimalist Program's restrictive framework, relying only on projection, not feature percolation crossing maximal projections, and on “Agree.” The chapter delineates the descriptive dimensions of pied‐piping primarily based onwh‐movement. It examines attested construction‐specific variation – namely,wh‐pied‐piping in restrictive and non‐restrictive relative clauses,wh‐questions, and free relatives – and explores structural properties of the phenomenon such as the phrase‐internal position of the pied‐piper, the category types of pied‐piped phrases, and non‐wh‐pied‐pipers. The related theoretical issues assessed include the locality/structural limitations on what can induce a pied‐piping effect, the “repair” nature of pied‐piping, the status of marked “massive” pied‐piping, and attested parametric variation. The chapter discusses feature percolation approaches and outlines two recent alternatives dispensing with the latter within a minimalist perspective.
Topic Prominence
Authors: Paul Waltraud , Whitman John 
Published: November 2017

AbstractWe assimilate the typological feature of topic prominence to established treatments of the left periphery. East Asian languages grouped together as topic‐prominent turn out to display important differences. In Japanese and Korean, the A‐domain extends higher than in Chinese, to include a fused FocusP/FiniteP projection. Descriptive properties sometimes associated with topic prominence include (1) obligatoriness of topics, (2) null topics, (3) overt spell‐out of the head of TopicP, (4)whin situ, (5) obligatory topicalization of generic DPs, (6) multiple topics, and (7) free ordering of argument and adjunct topics. However, all or most of these features can be found in non‐East Asian languages with an active left periphery, including full and residual V2 languages. The salient feature of the languages traditionally labeled topic‐prominent is that they do not fill the functional head of the Topic projection by movement; if at all, this head is filled by topic particles.
Honorifics
Authors: Hasegawa Nobuko 
Published: November 2017

AbstractJapanese is one of the rare languages that exhibit syntactically conditioned honorifics that interact with other syntactic processes. This chapter concentrates on such phenomena, and the following three honorific processes of Japanese are taken up: Subject Honorification (SH), where the subject is a target of the speaker's respect; Non‐Subject Honorification (NSH), in which the respect is paid to a non‐subject (i.e. an object, an indirect object, or the possessor of a(n in)direct object); and Hearer Honorification (HH), whose target of respect is the hearer. Although they have often been discussed and analyzed individually as different processes, this chapter, in addition to a concise description of the characteristics of these honorific processes and a review of representative previous analyses, provides an analysis of all three processes in terms of syntactic agreement between the honorific marking on the predicate and the nominal (DP) that is a target of respect.The following claims are particularly notable: (i) the locus of agreement is an honorific prefix (HP), which makes it possible to analyze not only verbal honorification but also nominal and adjective honorification basically as the same process. (ii) The case of multiple honorific marking of SH, involving the aspectual–such as(te)i(ru)‘progressive, perfective’ andhazime(ru)‘begin’ – is accounted for. (iii) NSH crucially involves Applicative Phrase (ApplP), which is equivalent to what takes place in the benefactive construction in Japanese, thereby capturing the phenomena observed in both constructions. The postulation of ApplP for NSH, furthermore, explains why the same HP on a predicate unambiguously agrees with a subject for SH, which does not involve ApplP, or a non‐subject for NSH. And (iv), by adopting the recent proposal that a matrix clause involves an extended clausal layer (e.g. a speech‐act layer), HH can be accounted for as a syntactic agreement process that involves this layer.