A formal theory of word order: a case study in West Germanic

This thesis has three primary goals . The first goal is to provide a treatrnent of bounded discontinuous constituency and word order in genera! and semi-free word order in particular. Bounded discontinuous constituency is taken to mean the kind of category-bounded discontinuity typically found in the German Mit­telfeld and in Dutch "cross-serial'' dependency constructions. It does not mean unbounded dependencies such as wh-movement. The second goal is to provide an alternative account of cross-linguistic variation in word order (particularly in West Germanic) to the Principles and Parameters approach of Government and Binding Theory. The third goal is to formalise the account in a single homogeneous logical formalism which is not based on rewrite rules or other formal language theoretic machinery

Evaluation and identification of leachables from the container closure system in ophthalmic product

In drug product packaging, migration of components from the container closure system into final formulation can compromise the therapeutic effect of the active pharmaceutical ingredient (API) or pose a health risk to the consumer. In response to this, regulatory expectations have elevated so that pharmaceutical companies show due diligence in the detection, quantitation, identification and monitoring of leachables through the shelf life of product. This work describes methods for the screening, quantification and identification of potential leachables in ophthalmic solutions. Particular focus was given to developing analytical separations using quality by design (QbD) principles. An ultra performance liquid chromatography (UPLC) method was developed for the analysis of 8 potential leachables in ophthalmic solutions. The method was optimized in the centre of a design space using fractional factorial design of experiments (DOE) ensuring baseline resolution while minimizing analytical run time. Repeatability validation studies were assessed using process capability (CpK) techniques. The test method was geometrically transformed to allow simultaneous analysis on high performance liquid chromatography (HPLC) test systems. Mass spectra were generated for the leachables using an electrospray ionization (ESI) ion trap mass spectrometer. An extraction and leachable study was executed on an ophthalmic solution under long term stability conditions in Chapter 3. The screening profile and concentration of leachables in the final drug product was monitored with consideration for time, temperature and humidity variables. The structural identity of any detected leachables were unknown and were tracked using their retention time relative to the reference standard. A single leachable was detected and the unidentified leachable was qualified through extraction of the packaging components from the container closure system (Stage I) and comparison to LC profile of the long term stability analysis (Stage II). The identification was confirmed using the LC-MS analytical method developed in Chapter 2. A single leachable, diethyl phthalate, identified using MS, was found to be present due to the adhesive used on the tamper evident seal packaging component. It was quantitated against a qualified reference standard at a maximum level of 8 ppm. The level of 8 ppm is below the allowed 10 ppm threshold level as stipulated by the FDA

A Reference Architecture for Natural Language Generation Systems

We present the RAGS (Reference Architecture for Generation Systems) framework: a specification of an abstract Natural Language Generation (NLG) system architecture to support sharing, re-use, comparison and evaluation of NLG technologies. We argue that the evidence from a survey of actual NLG systems calls for a different emphasis in a reference proposal from that seen in similar initiatives in information extraction and multimedia interfaces. We introduce the framework itself, in particular the two-level data model that allows us to support the complex data requirements of NLG systems in a flexible and coherent fashion, and describe our efforts to validate the framework through a range of implementations

Can we normalise developmentally appropriate health care for young people in UK hospital settings? An ethnographic study

OBJECTIVE: The WHO has argued that adolescent-responsive health systems are required. Developmentally appropriate healthcare (DAH) for young people is one approach that could underpin this move. The aim of this study was to explore the potential for DAH to become normalised, to become a routine, taken-for-granted, element of clinical practice. DESIGN: Qualitative ethnographic study. Analyses were based on procedures from first-generation grounded theory and theoretically informed by normalisation process theory. SETTING: Two tertiary and one secondary care hospital in England. PARTICIPANTS: 192 participants, health professionals (n=121) and managers (n=71) were recruited between June 2013 and January 2015. Approximately 1600 hours of non-participant observations in clinics, wards and meeting rooms were conducted, alongside 65 formal qualitative interviews. RESULTS: We observed diverse values and commitments towards the care of young people and provision of DAH, including a distributed network of young person-orientated practitioners. Informal networks of trust existed, where specific people, teams or wards were understood to have the right skill-mix, or mindset, or access to resources, to work effectively with young people. As young people move through an organisation, the preference is to direct them to other young person-orientated practitioners, so inequities in skills and experience can be self-sustaining. At two sites, initiatives around adolescent and young adult training remained mostly within these informal networks of trust. At another, through support by wider management, we observed a programme that sought to make the young people's healthcare visible across the organisation, and to get people to reappraise values and commitment. CONCLUSION: To move towards normalisation of DAH within an organisation, we cannot solely rely on informal networks and cultures of young person-orientated training, practice and mutual referral and support. Organisation-wide strategies and training are needed, to enable better integration and consistency of health services for all young people

Natural language processing in CLIME, a multilingual legal advisory system

This paper describes CLIME, a web-based legal advisory system with a multilingual natural language interface. clime is a 'proof-of-concept' system which answers queries relating to ship-building and ship-operating regulations. Its core knowledge source is a set of such regulations encoded as a conceptual domain model and a set of formalised legal inference rules. The system supports retrieval of regulations via the conceptual model, and assessment of the legality of a situation or activity on a ship according to the legal inference rules. The focus of this paper is on the natural language aspects of the system, which help the user to construct semantically complex queries using wysiwym technology, allow the system to produce extended and cohesive responses and explanations, and support the whole interaction through a hybrid synchronous/asynchronous dialogue structure. Multilinguality (English and French) is viewed simply as interface localisation: the core representations are languageneutral, and the system can present extended or local interactions in either language at any time. The development of clime featured a high degree of client involvement, and the specification, implementation and evaluation of natural language components in this context are also discussed

NO, ROS, and cell death associated with caspase-like activity increase in stress-induced microspore embryogenesis of barley

Under specific stress treatments (cold, starvation), in vitro microspores can be induced to deviate from their gametophytic development and switch to embryogenesis, forming haploid embryos and homozygous breeding lines in a short period of time. The inductive stress produces reactive oxygen species (ROS) and nitric oxide (NO), signalling molecules mediating cellular responses, and cell death, modifying the embryogenic microspore response and therefore, the efficiency of the process. This work analysed cell death, caspase 3-like activity, and ROS and NO production (using fluorescence probes and confocal analysis) after inductive stress in barley microspore cultures and embryogenic suspension cultures, as an in vitro system which permitted easy handling for comparison. There was an increase in caspase 3-like activity and cell death after stress treatment in microspore and suspension cultures, while ROS increased in non-induced microspores and suspension cultures. Treatments of the cultures with a caspase 3 inhibitor, DEVD-CHO, significantly reduced the cell death percentages. Stress-treated embryogenic suspension cultures exhibited high NO signals and cell death, while treatment with S-nitrosoglutathione (NO donor) in control suspension cultures resulted in even higher cell death. In contrast, in microspore cultures, NO production was detected after stress, and, in the case of 4-day microspore cultures, in embryogenic microspores accompanying the initiation of cell divisions. Subsequent treatments of stress-treated microspore cultures with ROS and NO scavengers resulted in a decreasing cell death during the early stages, but later they produced a delay in embryo development as well as a decrease in the percentage of embryogenesis in microspores. Results showed that the ROS increase was involved in the stress-induced programmed cell death occurring at early stages in both non-induced microspores and embryogenic suspension cultures; whereas NO played a dual role after stress in the two in vitro systems, one involved in programmed cell death in embryogenic suspension cultures and the other in the initiation of cell division leading to embryogenesis in reprogrammed microspores

Chemokine Lkn-1/CCL15 enhances matrix metalloproteinase-9 release from human macrophages and macrophage-derived foam cells

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCL15), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions play a crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCL15 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis

Health professionals' and managers' definitions of developmentally appropriate healthcare for young people:Conceptual dimensions and embedded controversies

Objectives: We aimed to (i) explore how health professionals and managers who work with young people seek to define developmentally appropriate healthcare (DAH), (ii) identify the range of conceptual dimensions present in their definitions and (iii) explore the controversies embedded in their characterisations of DAH. Methods: A qualitative multisite ethnographic study was conducted across three hospitals in England. We undertook face-to-face semi-structured interviews with health professionals and managers; and non-participant observation in clinics, wards and meetings. Anonymised field notes and interview transcripts were analysed using thematic analysis. The theme conceptualisations of DAH' was then further analysed, and the resulting themes categorised to form conceptual dimensions. Results: We recruited 192 participants and conducted 65 interviews (41 with health professionals and 24 with managers) and approximately 1600 hours of non-participant observations (involving 103 health professionals and 72 managers). Despite the wide range of definitions provided by participants, five conceptual dimensions of DAH were identified: (i) biopsychosocial development and holistic care, (ii) acknowledgement of young people as a distinct group, (iii) adjustment of care as the young person develops, (iv) empowerment of the young person by embedding health education and health promotion and (v) interdisciplinary and interorganisational work. Also, some controversies were identified within most dimensions. Conclusions: This study illustrates the lack of a generalised definition of DAH for young people among UK health professionals and managers, and presents a set of five core dimensions that can inform future research to help define and evaluate DAH for young people

Development of maternal seed tissue in barley is mediated by regulated cell expansion and cell disintegration and coordinated with endosperm growth

After fertilization, filial grain organs are surrounded by the maternal nucellus embedded within the integuments and pericarp. Rapid early endosperm growth must be coordinated with maternal tissue development. Parameters of maternal tissue growth and development were analysed during early endosperm formation. In the pericarp, cell proliferation is accomplished around the time of fertilization, followed by cell elongation predominantly in longitudinal directions. The rapid cell expansion coincides with endosperm cellularization. Distribution of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling)-positive nuclei reveals distinct patterns starting in the nucellus at anthesis and followed later by the inner cell rows of the pericarp, then spreading to the whole pericarp. The pattern suggests timely and spatially regulated programmed cell death (PCD) processes in maternal seed tissues. When the endosperm is coenocytic, PCD events are only observed within the nucellus. Thereby, remobilization of nucellar storage compounds by PCD could nourish the early developing endosperm when functional interconnections are absent between maternal and filial seed organs. Specific proteases promote PCD events. Characterization of the barley vacuolar processing enzyme (VPE) gene family identified seven gene members specifically expressed in the developing grain. HvVPE2a (known as nucellain) together with closely similar HvVPE2b and HvVPE2d might be involved in nucellar PCD. HvVPE4 is strongly cell specific for pericarp parenchyma. Correlative evidence suggests that HvVPE4 plays a role in PCD events in the pericarp. Possible functions of PCD in the maternal tissues imply a potential nutritive role or the relief of a physical restraint for endosperm growth. PCD could also activate post-phloem transport functions