7,730 research outputs found
Hypoxia-regulated glucose transporter Glut-1 may influence chemosensitivity to some alkylating agents: Results of EORTC (First Translational Award) study of the relevance of tumour hypoxia to the outcome of chemotherapy in human tumour-derived xenografts
Tumour hypoxia confers poor prognosis in a wide range of solid tumours, due to an increased malignancy, increased likelihood of metastasis and treatment resistance. Poorly oxygenated tumours are resistant to both radiation therapy and chemotherapy. However, although the link between radiation therapy and hypoxia is well established
in a range of clinical studies, evidence of its influence on chemotherapy response is lacking. In this study, a panel of human tumour-derived xenografts that have been characterised previously for in vivo response to a large series of anti-cancer agents, and have been found to show chemosensitivities that correlate strongly with the parent tumour, were used to address this issue. Immunohistochemistry was carried out on formalinfixed, paraffin-embedded sections of xenograft samples to detect expression of the intrinsic hypoxia marker Glut-1 and adducts of the bioreductive hypoxia marker pimonidazole. Glut-1 scores correlated significantly with T/C values for CCNU sensitivity (r=0.439, P=0.036, n=23) and showed a borderline significant correlation with dacarbazine T/C (r=0.405, P=0.076, n=20). However, there was no correlation between both Glut-1 and pimonidazole scores and T/C obtained for the bioreductive drug mitomycin C. The use of human tumour-derived xenografts offers a potentially useful way of using archival material to determine the influence of hypoxia and other tumour-microenvironmental factors on chemosensitivity without the direct use of human subjects
Integrating the promotion of physical activity within a smoking cessation programme: Findings from collaborative action research in UK Stop Smoking Services
Background: Within the framework of collaborative action research, the aim was to explore the feasibility of
developing and embedding physical activity promotion as a smoking cessation aid within UK 6/7-week National
Health Service (NHS) Stop Smoking Services.
Methods: In Phase 1 three initial cycles of collaborative action research (observation, reflection, planning,
implementation and re-evaluation), in an urban Stop Smoking Service, led to the development of an integrated
intervention in which physical activity was promoted as a cessation aid, with the support of a theoretically based
self-help guide, and self monitoring using pedometers. In Phase 2 advisors underwent training and offered the
intervention, and changes in physical activity promoting behaviour and beliefs were monitored. Also, changes in
clients’ stage of readiness to use physical activity as a cessation aid, physical activity beliefs and behaviour and
physical activity levels were assessed, among those who attended the clinic at 4-week post-quit. Qualitative data
were collected, in the form of clinic observation, informal interviews with advisors and field notes.
Results: The integrated intervention emerged through cycles of collaboration as something quite different to
previous practice. Based on field notes, there were many positive elements associated with the integrated
intervention in Phase 2. Self-reported advisors’ physical activity promoting behaviour increased as a result of
training and adapting to the intervention. There was a significant advancement in clients’ stage of readiness to use physical activity as a smoking cessation aid.
Conclusions: Collaboration with advisors was key in ensuring that a feasible intervention was developed as an aid to smoking cessation. There is scope to further develop tailored support to increasing physical activity and
smoking cessation, mediated through changes in perceptions about the benefits of, and confidence to do physical activity
On the infrared behaviour of 3d Chern-Simons theories in N=2 superspace
We discuss the problem of infrared divergences in the N=2 superspace approach
to classically marginal three-dimensional Chern-Simons-matter theories.
Considering the specific case of ABJM theory, we describe the origin of such
divergences and offer a prescription to eliminate them by introducing
non-trivial gauge-fixing terms in the action. We also comment on the extension
of our procedure to higher loop order and to general three-dimensional
Chern-Simons-matter models.Comment: 26 pages, 6 figures, JHEP3; v2: minor corrections and references
added; v3: introduction expanded, presentation of section 3.3.1 improved,
references added, version to appear in JHE
Growth dynamics and the evolution of cooperation in microbial populations
Microbes providing public goods are widespread in nature despite running the
risk of being exploited by free-riders. However, the precise ecological factors
supporting cooperation are still puzzling. Following recent experiments, we
consider the role of population growth and the repetitive fragmentation of
populations into new colonies mimicking simple microbial life-cycles.
Individual-based modeling reveals that demographic fluctuations, which lead to
a large variance in the composition of colonies, promote cooperation. Biased by
population dynamics these fluctuations result in two qualitatively distinct
regimes of robust cooperation under repetitive fragmentation into groups.
First, if the level of cooperation exceeds a threshold, cooperators will take
over the whole population. Second, cooperators can also emerge from a single
mutant leading to a robust coexistence between cooperators and free-riders. We
find frequency and size of population bottlenecks, and growth dynamics to be
the major ecological factors determining the regimes and thereby the
evolutionary pathway towards cooperation.Comment: 26 pages, 6 figure
Electrophysiological Correlates of Strategic Monitoring in Event-Based and Time-Based Prospective Memory
Prospective memory (PM) is the ability to remember to accomplish an action when a particular event occurs (i.e., event-based PM), or at a specific time (i.e., time-based PM) while performing an ongoing activity. Strategic Monitoring is one of the basic cognitive functions supporting PM tasks, and involves two mechanisms: a retrieval mode, which consists of maintaining active the intention in memory; and target checking, engaged for verifying the presence of the PM cue in the environment. The present study is aimed at providing the first evidence of event-related potentials (ERPs) associated with time-based PM, and at examining differences and commonalities in the ERPs related to Strategic Monitoring mechanisms between event- and time-based PM tasks
Anomalous structure in the single particle spectrum of the fractional quantum Hall effect
The two-dimensional electron system (2DES) is a unique laboratory for the
physics of interacting particles. Application of a large magnetic field
produces massively degenerate quantum levels known as Landau levels. Within a
Landau level the kinetic energy of the electrons is suppressed, and
electron-electron interactions set the only energy scale. Coulomb interactions
break the degeneracy of the Landau levels and can cause the electrons to order
into complex ground states. In the high energy single particle spectrum of this
system, we observe salient and unexpected structure that extends across a wide
range of Landau level filling fractions. The structure appears only when the
2DES is cooled to very low temperature, indicating that it arises from delicate
ground state correlations. We characterize this structure by its evolution with
changing electron density and applied magnetic field. We present two possible
models for understanding these observations. Some of the energies of the
features agree qualitatively with what might be expected for composite
Fermions, which have proven effective for interpreting other experiments in
this regime. At the same time, a simple model with electrons localized on
ordered lattice sites also generates structure similar to those observed in the
experiment. Neither of these models alone is sufficient to explain the
observations across the entire range of densities measured. The discovery of
this unexpected prominent structure in the single particle spectrum of an
otherwise thoroughly studied system suggests that there exist core features of
the 2DES that have yet to be understood.Comment: 15 pages, 10 figure
Dynamic modeling of mean-reverting spreads for statistical arbitrage
Statistical arbitrage strategies, such as pairs trading and its
generalizations, rely on the construction of mean-reverting spreads enjoying a
certain degree of predictability. Gaussian linear state-space processes have
recently been proposed as a model for such spreads under the assumption that
the observed process is a noisy realization of some hidden states. Real-time
estimation of the unobserved spread process can reveal temporary market
inefficiencies which can then be exploited to generate excess returns. Building
on previous work, we embrace the state-space framework for modeling spread
processes and extend this methodology along three different directions. First,
we introduce time-dependency in the model parameters, which allows for quick
adaptation to changes in the data generating process. Second, we provide an
on-line estimation algorithm that can be constantly run in real-time. Being
computationally fast, the algorithm is particularly suitable for building
aggressive trading strategies based on high-frequency data and may be used as a
monitoring device for mean-reversion. Finally, our framework naturally provides
informative uncertainty measures of all the estimated parameters. Experimental
results based on Monte Carlo simulations and historical equity data are
discussed, including a co-integration relationship involving two
exchange-traded funds.Comment: 34 pages, 6 figures. Submitte
Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells
Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator
Tensor hierarchies, Borcherds algebras and E11
Gauge deformations of maximal supergravity in D=11-n dimensions generically
give rise to a tensor hierarchy of p-form fields that transform in specific
representations of the global symmetry group E(n). We derive the formulas
defining the hierarchy from a Borcherds superalgebra corresponding to E(n).
This explains why the E(n) representations in the tensor hierarchies also
appear in the level decomposition of the Borcherds superalgebra. We show that
the indefinite Kac-Moody algebra E(11) can be used equivalently to determine
these representations, up to p=D, and for arbitrarily large p if E(11) is
replaced by E(r) with sufficiently large rank r.Comment: 22 pages. v2: Published version (except for a few minor typos
detected after the proofreading, which are now corrected
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