1,668 research outputs found
Kleist and the space of collapse
In 1800 the writer Heinrich von Kleist observed that an arch remains standing
because its stones all want to collapse at the same time. Rather than being an
empirical observation, Kleist’s proposition of the collapsing arch as a material
object made from cut stone which constructs space, inadvertently became a
poetic, and a trope for his later work as it contained the possibility of its own
disruption and demise. After reading Kant’s critical philosophy Kleist made a
traumatic transition from empirical to critical thinking. Kleist represented the
potential for collapse through the application of Kant’s premise of uncertainty
and in the unknowability of truth.
This thesis is practice-based and interdisciplinary. Novalis’s poetic, multidisciplinary,
experimental writing is referenced. The central inquiry theorises
collapse, uncertainty and experimentation through philosophical, historical,
material, architectural and conceptual thinking and in film and video making
as experimental practice. Through making 16mm films, videos and still
photography I explored and demonstrated collapse on the island of Portland in
Dorset, as an uncertain landscape where quarrying and landslips have rendered
much of the island as a space that can be viewed as one of collapse. Portland is
a site where material histories of place and histories of material in turn can be
traced on to the constructed, empty spaces as a disrupted landscape of collapse.
The quality of uncertainty pervades the island.
With reference to Kant, the first chapter analyses Kleist’s letter about the
collapsing arch as a material object and as epistolary philosophy. The second
chapter closely examines collapse as architectural, social, material, territorial
and spatial in two of Kleist’s stories and his compulsion towards the abyss. The
third chapter on materiality and collapse at Portland leads back to eighteenth
century theories of the earth, histories of geology and architecture, and the use
of stone. In the fourth chapter the film and video as situated practice synthesize
experimental thinking and practice as a poetic of collapse.
The exploration and experimentation with the concept of collapse in theory and
practice aims to demonstrate that collapse as imminence – potential and actual –
is internal and external, and that uncertainty creates the conditions of collapse in
time and space
The labor market regimes of Denmark and Norway – one Nordic model?
The literature on the Danish and Norwegian labor market systems emphasizes the commonalities of the two systems. We challenge this perception by investigating how employers in multinational companies in Denmark and Norway communicate with employees on staffing changes. We argue that the development of ‘flexicurity’ in Denmark grants Danish employers considerably greater latitude in engaging in staffing changes than its Nordic counterpart, Norway. Institutional theory leads us to suppose that large firms located in the Danish setting will be less likely to engage in employer–employee communication on staffing plans than their Norwegian counterparts. In addition, we argue that in the Danish context indigenous firms will have a better insight into the normative and cognitive aspects to flexicurity than foreign-owned firms, meaning that they are more likely to engage in institutional entrepreneurialism than their foreign owned counterparts. We supplement institutional theory with an actor perspective in order to take into account the role of labor unions. Our analysis is based on a survey of 203 firms in Norway and Denmark which are either indigenous multinational companies or the subsidiaries of foreign multinational companies. The differences we observe cause us to conclude that the notion of a common Nordic model is problematic
The AdS(5)xS(5) Semi-Symmetric Space Sine-Gordon Theory
The generalized symmetric space sine-Gordon theories are a series of
1+1-integrable field theories that are classically equivalent to superstrings
on symmetric space spacetimes F/G. They are formulated in terms of a
semi-symmetric space as a gauged WZW model with fermions and a potential term
to deform it away from the conformal fixed point. We consider in particular the
case of PSU(2,2|4)/Sp(2,2)xSp(4) which corresponds to AdS(5)xS(5). We argue
that the infinite tower of conserved charges of these theories includes an
exotic N=(8,8) supersymmetry that is realized in a mildy non-local way at the
Lagrangian level. The supersymmetry is associated to a double central extension
of the superalgebra psu(2|2)+psu(2|2) and includes a non-trivial R symmetry
algebra corresponding to global gauge transformations, as well as 2-dimensional
spacetime translations. We then explicitly construct soliton solutions and show
that they carry an internal moduli superspace CP(2|1)xCP(2|1) with both bosonic
and Grassmann collective coordinates. We show how to semi-classical quantize
the solitons by writing an effective quantum mechanical system on the moduli
space which takes the form of a co-adjoint orbit of SU(2|2)xSU(2|2). The
spectrum consists of a tower of massive states in the short, or atypical,
symmetric representations, just as the giant magnon states of the string world
sheet theory, although here the tower is truncated.Comment: 39 pages, references adde
R-mode oscillations and rocket effect in rotating superfluid neutron stars. I. Formalism
We derive the hydrodynamical equations of r-mode oscillations in neutron
stars in presence of a novel damping mechanism related to particle number
changing processes. The change in the number densities of the various species
leads to new dissipative terms in the equations which are responsible of the
{\it rocket effect}. We employ a two-fluid model, with one fluid consisting of
the charged components, while the second fluid consists of superfluid neutrons.
We consider two different kind of r-mode oscillations, one associated with
comoving displacements, and the second one associated with countermoving, out
of phase, displacements.Comment: 10 page
The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development
Background: The use of in vitro cell cultures is a powerful tool for obtaining key insights into the behaviour and response of cells to interventions in normal and disease situations. Unlike in vivo settings, in vitro experiments allow a fine-tuned control of a range of microenvironmental elements independently within an isolated setting. The recent expansion in the use of three-dimensional (3D) in vitro assays has created a number of representative tools to study cell behaviour in a more physiologically 3D relevant microenvironment. Complex 3D in vitro models that can recapitulate human tissue biology are essential for understanding the pathophysiology of disease. Aim: The development of the 3D coculture collagen contraction and invasion assay, the "organotypic assay," has been widely adopted as a powerful approach to bridge the gap between standard two-dimensional tissue culture and in vivo mouse models. In the cancer setting, these assays can then be used to dissect how stromal cells, such as cancer-associated fibroblasts (CAFs), drive extracellular matrix (ECM) remodelling to alter cancer cell behaviour and response to intervention. However, to date, many of the published organotypic protocols are low-throughput, time-consuming (up to several weeks), and work-intensive with often limited scalability. Our aim was to develop a fast, high-throughput, scalable 3D organotypic assay for use in oncology screening and drug development. Methods and results Here, we describe a modified 96-well organotypic assay, the "Mini-Organo," which can be easily completed within 5 days. We demonstrate its application in a wide range of mouse and human cancer biology approaches including evaluation of stromal cell 3D ECM remodelling, 3D cancer cell invasion, and the assessment of efficacy of potential anticancer therapeutic targets. Furthermore, the organotypic assay described is highly amenable to customisation using different cell types under diverse experimental conditions. Conclusions: The Mini-Organo high-throughput 3D organotypic assay allows the rapid screening of potential cancer therapeutics in human and mouse models in a time-efficient manner
Results of an open label feasibility study of sodium valproate in people with McArdle disease
McArdle disease results from a lack of muscle glycogen phosphorylase in skeletal muscle tissue. Regenerating skeletal muscle fibres can express the brain glycogen phosphorylase isoenzyme. Stimulating expression of this enzyme could be a therapeutic strategy. Animal model studies indicate that sodium valproate (VPA) can increase expression of phosphorylase in skeletal muscle affected with McArdle disease. This study was designed to assess whether VPA can modify expression of brain phosphorylase isoenzyme in people with McArdle disease. This phase II, open label, feasibility pilot study to assess efficacy of six months treatment with VPA (20 mg/kg/day) included 16 people with McArdle disease. Primary outcome assessed changes in VO2peak during an incremental cycle test. Secondary outcomes included: phosphorylase enzyme expression in post-treatment muscle biopsy, total distance walked in 12 min, plasma lactate change (forearm exercise test) and quality of life (SF36). Safety parameters. 14 participants completed the trial, VPA treatment was well tolerated; weight gain was the most frequently reported drug-related adverse event. There was no clinically meaningful change in any of the primary or secondary outcome measures including: VO2peak, 12 min walk test and muscle biopsy to look for a change in the number of phosphorylase positive fibres between baseline and 6 months of treatment. Although this was a small open label feasibility study, it suggests that a larger randomised controlled study of VPA, may not be worthwhile
Surfactant protein D modulates HIV infection of both T-cells and dendritic cells
Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo
Presence of clone-specific markers at birth in children with acute lymphoblastic leukaemia
Recent studies have suggested that development of childhood acute lymphoblastic leukaemia may often be initiated in utero. To provide further evidence of an prenatal origin of childhood leukaemia, we conducted a molecular biological investigation of nine children with B-precursor acute lymphoblastic leukaemia carrying the chromosomal translocation t(12;21), the most common subtype of all childhood acute lymphoblastic leukaemia. Specifically, for each child we identified the non-constitutive chromosomal sequences made up by the t(12;21) fusion gene. From these, leukaemia clone-specific DNA primers were constructed and applied in nested polymerase chain reaction analyses of DNA extracted from the patients' Guthrie cards obtained at birth. Leukaemia clone-specific fusion gene regions were demonstrated in Guthrie card DNA of three patients, age 2 years 11 months, 3 years 4 months, and 5 years 8 months at leukaemia diagnosis. Our findings are consistent with previous observations, and thus provide further evidence that the development of t(12;21) B-precursor acute lymphoblastic leukaemia may be initiated in utero. Review of the current literature moreover indicates that age at leukaemia may be inversely correlated with the burden of cells with leukaemia clonal markers, i.e. leukaemia predisposed cells at birth, and that certain types of childhood acute lymphoblastic leukaemia develop as a multiple step process involving both pre- and postnatal genetic events
Differential inflammasome activation predisposes to acute-on-chronic liver failure in human and experimental cirrhosis with and without previous decompensation
OBJECTIVE Systemic inflammation predisposes acutely
decompensated (AD) cirrhosis to the development of
acute-on-chronic liver failure (ACLF). Supportive treatment
can improve AD patients, becoming recompensated. Little is
known about the outcome of patients recompensated after
AD. We hypothesise that different inflammasome activation
is involved in ACL F development in compensated and
recompensated patients.
DESIGN 249 patients with cirrhosis, divided into
compensated and recompensated (previous AD), were
followed prospectively for fatal ACL F development. Two
external cohorts (n=327) (recompensation, AD and ACL F)
were included. Inflammasome-driving interleukins (ILs),
IL-1α (caspase-4/11-dependent) and IL-1β (caspase-1-
dependent), were measured. In rats, bile duct ligationinduced cirrhosis and lipopolysaccharide exposition were
used to induce AD and subsequent recompensation.
IL-1α and IL-1β levels and upstream/downstream gene
expression were measured.
RESULTS Patients developing ACL F showed higher
baseline levels of ILs. Recompensated patients and
patients with detectable ILs had higher rates of ACL F
development than compensated patients. Baseline
CLIF-C (European Foundation for the study of chronic
liver failure consortium) AD, albumin and IL-1α
were independent predictors of ACL F development
in compensated and CLIF-C AD and IL-1β in
recompensated patients. Compensated rats showed
higher IL-1α gene expression and recompensated rats
higher IL-1β levels with higher hepatic gene expression.
Higher IL-1β detection rates in recompensated patients
developing ACL F and higher IL-1α and IL-1β detection
rates in patients with ACL F were confirmed in the two
external cohorts.
CONCLUSION Previous AD is an important risk factor
for fatal ACL F development and possibly linked with
inflammasome activation. Animal models confirmed
the results showing a link between ACL F development
and IL-1α in compensated cirrhosis and IL-1β in
recompensated cirrhosi
Identification of coherent flood regions across Europe by using the longest streamflow records
This study compiles a new dataset, consisting of the longest available flow series from across Europe, and uses it to study the spatial and temporal clustering of flood events across the continent. Hydrological series at 102 gauging stations were collected from 25 European countries. Five geographically distinct large-scale homogeneous regions are identified: (i) an Atlantic region, (ii) a Continental region, (iii) a Scandinavian region, (iv) an Alpine region, and (v) a Mediterranean region. The months with a higher likelihood of flooding were identified in each region. The analysis of the clustering of annual counts of floods revealed an over-dispersion in the Atlantic and Continental regions, forming flood-rich and flood-poor periods, as well as an under-dispersion in the Scandinavian region that points to a regular pattern of flood occurrences at the inter-annual scale. The detection of trends in flood series is attempted by basing it on the identified regions, interpreting the results at a regional scale and for various time periods: 1900-1999; 1920-1999; 1939-1998 and 1956-1995. The results indicate that a decreasing trend in the magnitude of floods was observed mainly in the Continental region in the period 1920-1999 with 22% of the catchments revealing such a trend, as well as a decreasing trend in the timing of floods in the Alpine region in the period 1900-1999 with 75% of the catchments revealing this trend. A mixed pattern of changes in the frequency of floods over a threshold and few significant changes in the timing of floods were detected
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